A dissertation submitted to the Faculty of Medicine, University df the Witwatersrand in fulfilment of the requirements for the degree of Master of Science in Medicine Johannesburg 1992. / The objective of the research reported in this thesis was to describe the vaccination coverage of children aged 12 to 23 months in the Mosvold Health Ward of northern Kwa-Zulu. The Expanded Programme on Immunisation cluster sample technique was used. Simultaneous measurements of the children's weights and arm circumferences were done, and their birthplaces noted. Vaccination coverage rates were generally low; 74 to 83 per cent of the children had had BCG, 47 to 56 per cent had had three doses of DPT, 48 to 57 per cent had had three doses of polio and 47 to 56 per cent had had one dose of measles vaccine. Forty-eight per cent of the children had been born at home. Fifteen per cent had weights which Were more than two standard deviations below the median weight-for-age according to NCHS curves, 11 per cent had arm circumferences of 13,5 centimetres or less. The results are compared with other findings from else Where in southern Africa. Relevant literature on vaccination coverage improvement and the measurement thereof, is reviewed. Recommendations are made for increasing coverage rates in the Mosvold Health Ward) • / MT2017

RTX (Repeat in ToXin) superfamily consists of many proteins divided into several groups according to their different functions and characteristics: toxins, metalloproteases, lipases, proteins of the S-layer, bacteriocins and proteins with unknown function. However, all of them can be characterized by the following features: i) they contain tandemly repeated (6-50) nonapeptide glycine-rich calcium-binding consensus sequences GGXGXDX[L/I/V/W/Y/F]X (where X is any amino acid residue) in the C-terminal part of the protein. The presence of these repeats is a sine qua non condition for RTX protein family membership; ii) secretion from the cell occurs without a periplasmic intermediate by a mechanism which involves recognition of a signal sequence at the C-terminus of the protein by membrane-associated proteins that export the toxin across a channel spanning the entire bacterial envelope directly to the outside of the cell (Type I Secretion System); iii) the genes for protein synthesis, activation and secretion are mostly grouped together on the chromosome and form rtx operons. RTX toxins are the largest protein group of the RTX family. To this group belong mostly the proteins with molecular weight ranging from 100 to 200 kDa, with posttranslational fatty acid acylation mediated by a specific activating...

Introdução: As ações de imunização merecem destaque mundial pelo grande impacto do uso de vacinas na prevenção das doenças imunopreveníveis. A necessidade de um diagnóstico da prevalência de perdas vacinais constitui uma etapa fundamental para o gerenciamento de vacinas no município, permitindo organizar adequadamente o sistema, evitando assim desperdícios dos recursos públicos. Objetivo: Diagnosticar e caracterizar as perdas vacinais das Unidades Básicas de Saúde da Região Oeste do município de São Paulo. Método: Trata-se de um estudo descritivo, retrospectivo, quanti-qualitativo, no qual foi utilizado como abordagem metodológica o estudo de caso. A partir dos registros de movimentação de imunobiológicos e relatórios de doses aplicadas do ano de 2015, foi calculada a taxa total das perdas, prevalência das perdas técnicas, prevalência de perdas físicas e os motivos das perdas físicas, prevalência das perdas não categorizadas e a razão das doses aplicadas por doses utilizadas. Foram realizadas entrevistas com os funcionários das salas de vacina, das UBSs da Região Oeste do município de São Paulo. Resultados: A taxa total de perdas foi de 71,3 %, a prevalência de perda técnica 18,6% e a prevalência de perda física 28,4 %. Dentre os motivos das perdas físicas, obteve-se destaque para a falta de energia elétrica, representando 18,4 % das mesmas; as perdas não categorizadas totalizaram 24,2 %. Quanto à razão de doses aplicadas, por doses utilizadas, a vacina que apresentou o maior percentual de perdas foi a vacina BCG, visto que para cada dose aplicada foram perdidas 4,86 doses. Nas entrevistas realizadas com os profissionais que trabalham nas salas de vacina, observou-se que 60% deles acreditavam que a maior causa de perda vacinal em sua unidade se devia à perda técnica. Já 36,67 % referiram que a maior causa de perda se deveu às perdas físicas, causada por falta de energia elétrica. Os profissionais apontaram sugestões para minimizar as perdas vacinais; 50 % dos entrevistados relataram que a presença de vacinas unidoses amenizaria as perdas, 46,67 % dos profissionais sugeriram a existência de gerador elétrico e 16,67 % sugeriram o agendamento de vacinas com maior percentual de perda técnica. Conclusão: Os resultados demonstraram que a taxa total de perdas vacinais na Região Oeste do município de São Paulo foi de 71,3 % e na avaliação da prevalência de perdas, obteve-se uma maior prevalência de perdas físicas. Já na opinião dos profissionais entrevistados, a maior causa de perdas deveu-se às perdas técnicas. O presente trabalho propiciou a realização de uma cartilha educativa, que propõe ações que visem diminuir as perdas vacinais nas UBSs da Região Oeste do município de São Paulo. Essa cartilha será apresentada aos órgãos da Secretaria Municipal da Saúde de São Paulo, a saber: Coordenadoria de Saúde da Região Oeste (SUVIS Oeste) e Gerência de Imunização (COVISA). / Introduction: Immunization actions deserve worldwide focus due to the great impact of the use of vaccines in the foresight of immune preventable diseases. The need of prevalence of vaccine losses diagnosis constitutes a fundamental step for the vaccines management in the city, allowing the system adequate organization, therefore avoiding public resources waste. Objective: To diagnose and feature the vaccine losses at the basic health units of Sao Paulo\'s Western Area. Method: This is a descriptive, retrospective, quantitative-qualitative study, where the case study was used as a methodological approach. The total loss rate, the technical losses prevalence, the physical losses prevalence and the physical losses reasons proportion, the unclassified losses prevalence and the dose ratio applied by the doses used were calculated from the immune-biological records movement and dose reports for the year 2015. Interviews were carried out with the employees of the basic health units\' vaccine rooms of Sao Paulo\'s Western Area. Results: The total losses prevalence was of 71.3%, the technical loss prevalence was of 18.6%, the physical loss prevalence was of 28.4%. Of the reasons for physical loss, the lack of electricity represents 18.4%. Non-categorized losses totaled 24.2%. Regarding the dose ratio applied by doses used, the vaccine that presented the highest percentage was the BCG vaccine, for each applied dose there is a loss of 4.86 doses; regarding Yellow Fever vaccine, for each applied dose, 1.63 doses are lost; as for the Triple Viral vaccine, for each applied dose, 1.31 doses are lost. From the interviews with vaccine rooms employees, it was observed that 60% of them believe that vaccine loss greatest reason in their unit is due to technical loss, and 36.67% reported that the greatest cause of loss, it is due to physical loss caused by lack of electricity. The employees gave suggestions to minimize vaccine losses; 50% of the interviewees reported that the presence of unit dose vaccines would reduce losses, 46.67% of the employees suggested the need of an electric generator, and 16.67% suggested scheduling vaccines which have a higher percentage of technical loss. Conclusion: The results showed that the vaccine losses total rate in São Paulo\'s Western Area was of 71.3%, and that in the losses prevalence evaluation, a higher prevalence of physical losses was obtained, as for the opinion of employees interviewed, the greatest cause of loss is due to technical losses. Vaccine losses monitoring is important in order to find new alternatives for the production and distribution of immune-biological agents in order to reduce losses without missing the opportunity to vaccinate. The present work led to the realization of an educational booklet, which will propose actions aimed at reducing vaccine losse at the Health Basic Units of Sao Paulo\'s West Region. This booklet will be presented to Sao Paulo\'s City Health Department agencies, namely: Western Region Health Coordination (SUVIS Oeste) and Immunization Management (COVISA).

Este estudo tem por objetivo compreender as experiências de famílias com a vacinação de crianças menores de dois anos, fundamentado no cuidado em saúde, buscando subsídios para o cuidado de enfermagem. O reconhecimento da relação entre cuidado em saúde e a prática de vacinação permite enriquecer nossas intervenções. As bases conceituais estão centradas nos estudos sobre o cuidado e a reconstrução das práticas de saúde de J.R. Ayres. O substrato empírico consiste de entrevistas gravadas nos domicílios de 19 famílias moradoras na área de abrangência de duas unidades básicas de saúde do município de Franca-SP. A partir de abordagem qualitativa, na perspectiva hermenêutica, os dados foram analisados e agrupados ao redor de quatro temas: o cotidiano do cuidar da criança; conhecimentos práticos e científicos sobre vacinação de crianças; responsabilidade e obrigatoriedade da vacinação de crianças; e ampliação das práticas de vacinação de crianças. De modo geral, espontaneamente, a vacinação não é lembrada entre os cuidados familiares dispensados às crianças. As práticas em vacinação se estabeleceram numa relação de obrigatoriedades e, nessa construção, vários aspectos influenciaram as relações nas salas de vacina entre famílias e trabalhadores de saúde, particularmente de enfermagem. A prática de vacinação aparece descolada dos cuidados cotidianos da criança. A análise permitiu identificar elementos potenciadores da não vacinação: a inexperiência e dependência no empenho dos pais, estado civil solteira, excesso de tarefas, recusa de aplicações simultâneas de vacinação e a relação com os serviços de saúde (assistência fragmentada, ausência de diálogos, discriminação, falsas contra-indicações e relação embasada na obrigatoriedade) e elementos potenciadores da vacinação: ter experiência e realização pessoal no papel de ser pai/mãe, temor ao adoecimento, reconhecer como um bom cuidado, possuir conhecimento prático e científico de vacina e de manejo com eventos adversos e a relação com os serviços de saúde (acesso assegurado, flexibilidade do horário, vínculo, divulgação, gratuidade, posse do cartão de vacinas, campanhas de vacinação, disponibilização de vacinas e profissionais). As famílias entrevistadas sugerem as seguintes estratégias de aproximação às crianças/famílias que faltam à vacinação: informações pelos meios de comunicação, cartazes, seguimento de crianças, visita domiciliar e envolvimento de profissionais e serviços de outras áreas. O modo como as famílias cuidam da vacinação das crianças pode estar ligado ao modo de ser daquelas pessoas e ao modo como as práticas estão organizadas, demonstrando a necessidade de integração entre prática de vacinação e cuidado à saúde da criança nos serviços de atenção primária à saúde. Nesse sentido, é preciso reconstruir a prática de enfermagem em salas de vacinação, com vistas a articular saberes técnicos e saberes práticos. / This study aims to understand families experiences in vaccinating children under two years old, from a health care perspective, with a view to supporting nursing care. The acknowledgement of the relation between health care and vaccination practice makes it possible to enrich our interventions. The conceptual bases are centered on studies about care and the reconstruction of health practices by J.R. Ayres. The empirical substrate consists of interviews recorded at the homes of 19 families who lived in the area covered by two basic health units in Franca-SP, Brazil. Based on a qualitative approach, within a hermeneutical perspective, data were analyzed and grouped around four themes: daily care for the child; practical and scientific knowledge on vaccination for children; responsibility and obligation of vaccination for children; and broadening the vaccination practices for children. In general, spontaneously, vaccination is not remembered as a part of family care for children. Vaccination practices were established in a relation marked by obligations and, in this construction, various aspects influenced the relations between families and health professionals, particularly nursing staff, in the vaccination rooms. Vaccination appears to be separated from daily care for the child. The analysis allowed us to identify elements that enhance non-vaccination: inexperience and dependence in the parents? efforts, single civil status, excess tasks, refusal to receive simultaneous vaccination application and the relation with health services (fragmented care, absence of dialogues, discrimination, false contraindications and relation based on obligation) and elements enhancing vaccination: possessing experience and personal realization in the role of being a father/mother, fear of disease, acknowledging vaccination as good care, having practical and scientific knowledge about vaccination and coping with adverse events and the relation with health services (guaranteed access, flexible times, bonding, dissemination, no cost, possession of vaccination card, vaccination campaigns, availability of vaccines and professionals). The interviewed families suggest the following strategies to approach children/families who do not attend vaccination: information through communication means, posters, follow-up of children, home visits and involvement by professionals and services from other areas. The way families take care of the children s vaccination can be related to their way of being and to the way health practices are organized, demonstrating the need for integration between vaccination practice and child health care in primary care services. In this sense, nursing practices in vaccination rooms need to be reconstructed, with a view to articulating technical and practical knowledge.

Rotavirus is the most common cause of severe gastroenteritis among children <5 years of age worldwide and is responsible for 453,000 deaths among children in this age group. More than half of these deaths occur in sub-Saharan Africa. Because of the tremendous global burden of rotavirus, vaccine development and introduction has been a high priority for several international agencies, including the World Health Organization (WHO) and GAVI. Two live, attenuated, orally administered rotavirus vaccines, a pentavalent bovine-human reassortant vaccine (RV5; RotaTeq® (Merck and Co, Inc, Pennsylvania)) and a monovalent vaccine (RV1; Rotarix™ (GSK Biologicals, Rixensart, Belgium)) based on a human rotavirus strain, are licensed and available for use in many countries worldwide. Pre-licensure clinical trials of each of these vaccines in high and middle-income countries demonstrated high efficacy (85-98%) against severe rotavirus disease. Further studies conducted in low-income countries of Asia and Africa found modest efficacy (50%-70%) of these vaccines against severe rotavirus disease. However, the public health impact of vaccination (in terms of burden of severe rotavirus disease prevented by vaccinating a given number of children) is greater in developing countries because of the substantially higher baseline rotavirus disease burden in these settings. In 2009, the World Health Organization recommended the inclusion of rotavirus vaccine in the national immunization programs of all countries globally and particularly in those countries with high child mortality due to diarrhea. Of the 16 countries recently approved by GAVI for rotavirus vaccine introduction, 12 countries are located in Africa. As rotavirus vaccines are introduced into national immunization programs, monitoring their impact is a high priority for several reasons. There is a need to assess the effectiveness of these vaccines in routine use to ensure it parallels that of pre-licensure trials, particularly when used in developing countries. Assessing the impact of vaccination on disease burden in countries such as Rwanda will be vital to understanding the full public health benefit of the vaccine. The primary purpose of this program evaluation is to determine the impact of pentavalent rotavirus vaccine on rotavirus and all-cause diarrhea morbidity following introduction into the national immunization program in Rwanda in May 2012. Additionally, this evaluation will document changes in circulating strains over time pre- and post-vaccine introduction. It will also strengthen support for economic evaluation of treating diarrhea versus introduction of new vaccine in routine immunization. Methodology Various studies have been implemented since 2011 in the health sector in Rwanda to reach the goal of this thesis. First, we analyzed data for all-cause, non-bloody diarrheal disease among children <5 years of age from the routine health management information system (HMIS) in Rwanda from January 2008 through December 2011, The objective of this analysis was to determine whether routinely collected health information on national diarrhea hospitalizations, in-hospital deaths, and outpatient visits can be used to monitor the impact of rotavirus vaccine. We used data from the health management information system (HMIS) in Rwanda to describe trends in all-cause, non-bloody diarrhea hospitalizations and outpatient visits among children <5 years of age from 2008 to 2011 prior to vaccine introduction. Second, we evaluated the economic burden attributable to hospitalization for diarrhea among children aged less than 5 years in Rwanda. This was a prospective costing study where medical records and hospital bills for children admitted with diarrhea at 3 hospitals were collected to estimate costs. Interviews with the child’s caregivers provided medical costs incurred before and after hospitalization and the household costs. Third, we analyzed and tried to understand the introduction and delivery cost per dose or per child of the three new vaccines in Rwanda including the rotavirus vaccine for domestic and external financial resource mobilization. Fourth, we determined the rotavirus prevalence rates and circulating genotypes directly pre- and post-introduction of the RotaTeq rotavirus vaccine in May 2012. Stool samples were collected from 1,847 children <5 admitted to 8 surveillance sites for acute gastroenteritis (AGE) and tested for rotavirus antigens by enzyme immunoassay. Fifth, to monitor the effect of rotavirus vaccine in Rwanda, we studied trends in the number of hospital admissions for diarrhea and rotavirus before and after the introduction of the rotavirus vaccine. We conducted a time-series analysis to examine trends in admissions to hospital for non-bloody diarrhea in children younger than 5 years in Rwanda between Jan 1, 2009, and Dec 31, 2014, using monthly discharge data from the HMIS.Result All-cause, non bloody diarrheal hospitalizations and outpatient visits among children <5 years of age in Rwanda from 2008 to 2011 peaked during the June to August dry season, coinciding with the rotavirus season. The bulk of the diarrheal disease burden occurred in children <1 year of age. Average medical costs for each child for the hospitalization were $44.22 ± $23.74 and the total economic burden per hospitalization was $101, of which 65% was borne by the household. The unit cost of introducing rotavirus vaccines 2012 was 22.69 US. Among the 397 stool samples that were genotyped, 5 G types (G1, G4, G8, G9, and G12) and 3 P types (P[4], P[6], and P[8]) were identified. G8 (30.3%), G9 (28.0%), and G1 (19.7%) were the most prevalent G types, while P[8] (52.0%) and P[4] (32.6%) were the most prevalent P types. There was a significant amount of mixed G genotypes (12.1%), while mixed P types were less common (5.1%). G8P[4], G9P[8], and G1P[8] were the most prevalent strains, accounting for 27.8%, 24.3%, and 15.3% of all specimens, respectively.Compared with the 2009–11 pre vaccine baseline, hospital admissions for non-bloody diarrhea captured by the HMIS fell by 17–29% from a pre-vaccine median of 4051 to 2881 in 2013 and 3371 in 2014, admissions for AGE captured in pediatric ward registries decreased by 48–49%, and admissions specific to rotavirus captured by active surveillance fell by 61–70%. The greatest effect was recorded in children age-eligible to be vaccinated, but we noted a decrease in the proportion of children with diarrhea testing positive for rotavirus in almost every age group.ConclusionGiven the stable and consistent trends and the prominent seasonality consistent with that of rotavirus, HMIS data should provide a useful baseline to monitor rotavirus vaccine impact on the overall diarrheal disease burden in Rwanda. Active, sentinel surveillance for rotavirus diarrhea will help interpret changes in diarrheal disease trends following vaccine introduction. Other countries planning rotavirus vaccine introduction should explore the availability and quality of their HMIS data.Households often bear the largest share of the economic burden attributable to diarrhea hospitalization and the burden can be substantial, especially for households in the lowest income quintile.The cost of introduction of new vaccines (rotavirus) is less than the cost of treating the diarrhea diseases. The number of admissions to hospital for diarrhea and rotavirus in Rwanda fell substantially after rotavirus vaccine implementation, including among older children age-ineligible for vaccination, suggesting indirect protection through reduced transmission of rotavirus. These data highlight the benefits of routine vaccination against rotavirus in low-income settings. / Doctorat en Santé Publique / info:eu-repo/semantics/nonPublished

Sterile triploid Atlantic salmon represent a solution to the issues of pre-harvest sexual maturation and mature escapees from open aquaculture systems. Although the initial problems of reduced performance and increased deformities in triploids have been thoroughly researched, there is a continued lack of information on their susceptibility and response to disease and routine on-farm treatments compared to diploids. Thus, the main aim of this thesis was to enhance the current understanding of triploid health and immunity through experimental disease challenges and treatments, and aid in determining their robustness and, therefore, suitability for aquaculture. A commercial furunculosis vaccine equally protected diploids and triploids against challenge with Aeromonas salmonicida, and adhesion scores were similar between ploidy (Chapter 2). Interestingly, triploids had lower white blood cell counts but increased cellular activity, e.g. respiratory burst, compared to diploids. Following experimental cohabitation infection with Neoparamoeba perurans, causative agent of Amoebic Gill Disease (AGD), ploidy did not affect the manifestation or severity of AGD-associated gill pathology, or the serum innate immune response (Chapter 3). Hydrogen peroxide, used to treat against parasitic diseases, elicited similar primary and secondary stress responses in both ploidy, but led to differences in the expression of stress (cat, gpx1, gr, hsp70, sod1, sod2) and immune (saa5, crp/sap1a, crp/sap1b, il1β) genes (Chapter 4). Finally, vaccination with different vaccine treatments (4 commercial vaccines, 6 different vaccine combinations and a sham-vaccinated control) showed no ploidy differences in adhesion score or antibody response, although vertebral deformities remained higher in triploids (Chapter 5). Increasing severity of vaccine treatments negatively affected weight, length and thermal growth coefficient in both ploidy. Triploids were heavier than diploids at smolt (+ 14 %) and post smolt (+ 32 %). Overall, this research shows that triploid Atlantic salmon respond as well as diploids to disease and treatment challenges, and supports their application into full-scale commercial aquaculture.

Resumo: O tambaqui, Colossoma macropomum, é a espécie de maior importância na piscicultura amazônica. Entretanto, a sua criação tem enfrentado problemas com relação a perdas provocadas pela instalação de doenças que surgem com a intensificação do cultivo. Por isso, o tambaqui foi escolhido como modelo experimental nesta tese. Inicialmente foi avaliado o emprego dos imunoestimulantes 'beta'-glucano e nucleotídeos na dieta do tambaqui sobre o desempenho produtivo, respostas fisiológicas, imunológicas e resistência frente ao desafio com Aeromonas hydrophila, cujos resultados são apresentados no capítulo II. Os resultados deste estudo permitiram estabelecer que a suplementação de 'beta'-glucano e nucleotídeos na dieta do tambaqui não influenciam o desempenho produtivo; que o desafio bacteriano promoveu anemia normocítica-normocrômica ( 'beta'-glucano) e anemia macrocítica-hipocrômica (nucleotídeos); que a suplementação de 'beta'-glucano não alterou a concentração e atividade de lisozima e a de nucleotídeos determinou redução na atividade respiratória de leucócitos, e que a menor suplementação dos imunoestimulantes (0,1% de -glucano e 0,2% de nucleotídeos) promoveu maior sobrevivência para a espécie após o desafio com Aeromonas hydrophila. No capítulo III da tese avaliou-se as respostas fisiológicas de estresse de tambaquis alimentados com dietas suplementadas com 'beta'-glucano ou nucleotídeos após transporte em sistema fechado. Os resultados deste estudo permitiram estabelecer que as alterações dos parâmetros hematológicos, bioquímicos e imunológicos (atividade respiratória de leucócitos) ocorreram imediatamente após o transporte, com retorno aos níveis basais após 24 e 48 horas de recuperação. Entretanto, a suplementação de 'beta'-glucano ou nucleotídeos... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The Colossoma macropomum is the most farmed species in the Amazon region. Therefore, disease has been a significant problem in tambaqui culture with overcrowding. Thus, the tambaqui was chosen as experimental model in this work. First it was to evaluate the use of the immunostimulants 'beta'-glucan and nucleotide in the tambaqui diet on the productive performance, physiological and immunological responses and resistance of Aeromonas hydrophila challenge exposed into chapter II. These results provide that the 'beta'-glucan and nucleotide dietary supplementation had no influence on the productive performance; that the bacterial challenge promoted normocytic-normochromic anemia ( 'beta'-glucan) and macrocytichipocromic anemia (nucleotide); that the 'beta'-glucan supplementation did not change the lysozime concentration and activity; the nucleotide supplementation determinate the reduction of burst activity of leukocyte and the lowest concentrations of both immunoestimulants (0.1% -glucan and 0.2% nucleotide) were effective to secure higher survival of tambaqui when challenged with Aeromonas hydrophila. After, was to evaluate the physiological stress response of tambaqui fed with 'beta'-glucan or nucleotide supplemented diet after transportation in closed system, exposed into chapter III. The results of this study demonstrated that the alteration in the hematological, biochemical and immunological (oxidative burst of leukocyte) occurred immediately after the transportation and returned to base levels after 24 and 48 hours to recover. However the -glucan and nucleotide supplementation did not reduce the stress responses. In the last, the adjuvant effect of 'beta'-glucan in the efficiency of oil vaccine against Aeromonas hydrophila for tambaqui juveniles in the hematological responses, the concentration and activity... (Complete abstract click electronic access below) / Orientador: Flávio Ruas de Moraes / Coorientador: Fabiana Pilarski / Banca: Elisabeth Criscuolo Urbinati / Banca: Cleni Mara Marzocchi Machado / Banca: Marco Antonio de Andrade Belo / Banca: Margarida Maria Barros / Doutor

Dissertation is about the problems with vaccination of children, whose part is also the inoculation against tuberculosis. The objective is the analysis of opinions and approaches of parents toward the problems with vaccination of children in Czech Republic and to discover the level of their knowledge about tuberculosis disease and about vaccination against it. To get the information needed, the anonymous questionary has been used. In the first part we will familiarize ourselves with the main terms from the area of vaccination and also about tuberculosis's basic data. The second part includes presentation of data collected, which are sorted into the bars and graphs. It includes also the calculation of coefficient of benefit for area vaccination against tuberculosis. In the conclusion of work is the summary of collected data and their rating

Drug resistance is one of the most medically relevant forms of pathogen evolution. To date, vaccines have not failed with the same depressing regularity as drugs. Does that then make vaccines evolution-proof? In the face of vaccination, pathogens are thought to evolve in two ways: by evolving epitope changes at the antigenic target of vaccination (epitope evolution); or by evolving changes at other antigenic loci, some of which may involve virulence (virulence evolution). The fundamental difference between these two forms of evolution is that virulence evolution could lead to disease outcomes in unvaccinated people that are more severe than would have been seen prior to evolution. One of the theoretical assumptions of virulence evolution is that more virulent parasites will have a selective advantage over less virulent parasites in an immunized host, and are thus more likely to be transmitted. The assumption is that more virulent parasites may be competitively more superior in mixed infections, or may be better able to evade/modulate the host immune response. Thus, the aim of this thesis was to experimentally test whether more virulent parasites have a within-host selective advantage in an immunized host or whether vaccine efficacy is more likely to depend on genetic differences at the targeted sites of vaccination. I used clones (genotypes) of the rodent malaria Plasmodium chabaudi originally derived from wild-caught Thicket (Thamnomys rutilans) rats to infect laboratory mice and a rodent analogue of the candidate blood-stage malaria vaccine apical membrane antigen 1 (AMA-1). I found that within-host selection did not depend on parasite virulence, and that protective efficacy depended on genotype-specific differences at the vaccine target. Vaccine-induced protection was not enhanced by including a number of allelic variants. However, such genotype-specific responses were only observed when the vaccine was tested against genetically distinct P. chabaudi parasites. When one P. chabaudi genotype was serially passaged through naïve mice the derived line was more virulent and was subsequently less well controlled by vaccine-induced immunity. In other experiments I found within host competition not to be immune-mediated. Thus my results suggest that vaccination has the potential to select for more virulent parasites but that the selective advantage is likely to be independent of competition. The selective advantage may be attributable to the enhanced immune evasion of more virulent parasites. However, without genetic markers of virulence, the mechanisms that mediate this selection remain unknown. My thesis contributes towards a growing body of evidence that vaccines have the potential to differently alter the within-host parasite dynamics of particular pathogen genotypes and that the selection imposed is likely to be system specific, depending on the fine specificity of the vaccine-induced responses and the identity of infecting parasites. Although vaccine potency may not be enhanced by including more than one allelic variant of an antigen, multi-valent vaccines may be one of the best ways to avoid the inadvertent selection for more virulent malaria parasites.

Background: In Utah, all major hospital facilities have employee vaccination policies. However, the presence of health care worker vaccination policies in the Utah outpatient oncology setting was unknown. Objectives: The objectives were to identify Utah oncology outpatient employee vaccination policies and to identify what consequences, if any, were present for unvaccinated employees. Methods: This was a cross-sectional, descriptive study design in which clinic managers from outpatient oncology clinics in Utah were asked, via questionnaire, to describe the clinic's employee vaccination policy and the consequences for refusing the policy. Findings: Most vaccination policies applied to employees primarily assigned to work in the back office area. Most commonly, influenza and Hepatitis B vaccines were required as part of the vaccination policy. Most managers offered free vaccinations to employees, although most managers also allowed employees to refuse to follow the vaccination policy for medical, religious, or personal reasons.