A thesis completed by published work, Submitted to the School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the degree of Doctor of Philosophy Johannesburg, South Africa December 2016. / Introduction With the largest epidemic in the world, the consequences of human immunodeficiency virus (HIV) in South Africa extend far beyond its disease burden. In fact, patterns of HIV-related infection and mortality in South Africa still reflect social cleavages and inequalities. Similarly, poverty-related issues such as poor education, unemployment and subsequent low socio-economic status, rural residence and inadequate access to health care are all implicated in human papillomavirus (HPV) associated cervical cancer-related mortality (of which South Africa also has the highest globally). Despite the knowledge of reproductive functions and sexuality being poor among adolescents in South Africa, the majority commence their sexual activity early with an estimated national average of 15 years for girls and 14 years for boys. Further, many South African adolescents engage in sexual risk-taking behaviours including concurrent partners and unprotected sexual acts that considerably increase their vulnerability to sexually transmitted infections including HIV and HPV. In recognising the unique health needs of adolescents in South Africa, the national government has already pin-pointed school health services as a strategic arm of primary health care re-engineering. The aim of this body of work is to elaborate on restructuring of adolescent health care by introducing the HIV and HPV vaccine concomitantly in South Africa via a school-based sexual and reproductive health service. Methodology Data from four studies were analysed and are presented in three published and two unpublished papers. The first study evaluated the synergism between HIV and HPV in the South African context and formed the basis of the literature review. The second study considered HIV vaccine implementation alone. The third study assessed dual HIV and HPV vaccine strategies among females and the final study compared the dual vaccination strategy against recognised biomedical HIV prevention interventions. The studies evaluated the implementation of a hypothetical HIV vaccine and the bivalent HPV vaccine both individually and in combination when administered to school-going adolescents in South Africa. The health outcomes and the cost-effectiveness of these strategies were assessed. Assumptions were made regarding the hypothetical HIV vaccine (based on HIV vaccine studies conducted to date) including a coverage rate of 60% (uncertainty range: 30-70%), vaccine efficacy of 50% (uncertainty range: 30-70%) and vaccine price per dose of US$ 12 (uncertainty range: US$ 3-24). The uncertainty ranges were tested in the sensitivity analysis. Mortality statistics, disease transition parameters (for the individual diseases and the models representing joint disease) and HPV vaccine characteristics were drawn from the South African literature. The joint effectiveness of the dual vaccine strategy was considered multiplicative. Nine year old adolescents attending South African schools in 2012 were eligible for the intervention (vaccination) that was introduced opportunistically as part of the national health initiative introducing school-based sexual and reproductive health services. The learners were targeted prior to their reported sexual debut. The HIV vaccine was considered against the comparator of HIV counselling and testing (HCT) and the national roll-out of antiretroviral therapy (ART) that constituted the standard of care in South Africa. The HPV vaccine was modelled as prevention against HPV-related cervical cancer and pre-cancerous HPV-related cervical states. The health service provider (provider) perspective was adopted and the cohort was modelled through a lifetime horizon of 70 years with annual cycles. The economic costs and health outcomes were discounted at 3% with an uncertainty range between 0% and 6% assessed. Cost valuations were for 2012 and costs were adjusted to this common year. The quality-adjusted life year (QALY) was used as the outcome measure of health related quality of life and was used to calculate the incremental cost-effectiveness ratio (ICER) of the comparator against the vaccination interventions. The core model was a semi-Markov simulation with annual cycles. The study population entered the model HIV and HPV disease free and were exposed to the risk of acquiring each disease annually. The model structure was parameterised drawing from South African data available in the literature. One-way sensitivity analyses evaluated the impact of single assumptions on cost and outcomes. Probabilistic sensitivity analysis (PSA) with a bootstrapping technique explored the uncertainty in the model and evaluated the robustness of the results. The PSA data generated determined if the intervention fell below the willingness-to-pay (WTP) threshold. As South Africa does not have a pre-defined WTP threshold, the Gross Domestic Product (GDP) per capita (for 2012) was used as a proxy in accordance with the World Health Organization’s Guide to Cost-Effective Analysis. Additionally, benchmark interventions were used in the final comparison study as a measure of cost-effectiveness. Ethical approval for the study was obtained from the Human Research Ethics Committee (Medical) of the University of the Witwatersrand. Findings The second study explored the implementation of the HIV vaccine on an individual and national, programmatic level. The simultaneous implementation of HIV vaccination services with current HIV management programmes would be cost-effective, even at relatively higher vaccine cost. At base vaccine cost of US$ 12, the ICER was US$ 43 per QALY gained, with improved ICER values yielded at lower vaccine costs. The ICER was sensitive to the duration of vaccine-mediated protection and to variations in the vaccine efficacy. Data from this work demonstrate that vaccines offering longer duration of protection and at lower cost would result in improved ICER values. Assessing this HIV vaccine model on a national programmatic level, yielded an ICER of US$ 5 per life-year gained (LYG) (95% CI US$ 3-12) compared with the comparator. This fell considerably below the national WTP threshold of cost-effectiveness. This also translated to an 11% increase in per capita costs from US$ 80 to US$ 89. National implementation of this intervention could potentially result in an estimated cumulative gain of 24 million years of life (95% CI 8–34 million years) among those adolescents aged between 10-19 years that were vaccinated. The 10 year absolute risk reduction projected by HIV vaccine implementation was 0.42% for HIV incidence and 0.41% for HIV mortality. The ICER was sensitive to the HIV vaccine efficacy, coverage and vaccine pricing in the sensitivity analysis. The third study assessed the impact of dual HIV and HPV implementation strategies. Programmes that involved the dual vaccine strategy were assessed as cost-saving. ICER values were sensitive to the HIV vaccine cost. The dual vaccine strategy resulted in 10 year absolute risk reductions in HIV incidence (5.24%), dual mortality (1.21%) and a reduction in HPV incidence (0.39%) compared with no vaccination. Importantly, the reduction in HIV incidence rate and dual mortality rate in the dual vaccine strategy exceeded the reductions noted with the use of the HIV vaccine alone. All scenarios assessed with the dual vaccine strategy were cost-effective. Lower vaccine prices and reduced discount rates were associated with improved ICER outcomes. The final study compared the biomedical interventions of oral pre-exposure prophylaxis (PrEP), voluntary medical male circumcision (VMMC) and the scaling-up of ART coverage against the vaccine strategies. When compared with other biomedical HIV prevention interventions, the dual vaccination intervention was the most cost-effective strategy (US$ 7 per QALY gained) and averted 29% of new HIV infections. VMMC (US$ 30 per QALY gained) proved more cost-effective than HIV vaccination alone (US$ 93 per QALY gained), though VMMC averted 6% more new infections than the HIV vaccine. PrEP interventions were the least cost-effective. Combined dual vaccination and VMMC strategies represent the only dominant intervention. Strategies involving oral PrEP were the least cost-effective. Conclusion The findings of this thesis have implications for school-based adolescent health care and HIV- and HPV-related disease prevention among adolescents, a highly susceptible population. The cost-effectiveness of the dual HIV and HPV vaccine strategy was demonstrated, and the improved health outcomes associated with the interventions quantified. Proposals were suggested regarding possible combinations of HIV prevention interventions that could yield the favourable health outcomes with the most efficient use of financial resources. Several important areas for future research were identified to shed light on improving adolescent health care and for optimising HIV prevention strategies. These include integrating HIV and HPV services as part of the re-engineering of primary health care in South Africa, and then formulating economic evaluations of HIV/HPV prevention strategies targeting adolescents specifically. Further, more effective methods of collecting data on socially marginalised populations such as young people need to be explored. Another vital research area is the discussion and implementation of existing school health documents with the ideals embodied in the school health programme envisaged under the National Health Insurance restructuring. Once these are integrated, the cost implication of the combined programmes need to be assessed. / MT2017

Orientadores: Jose Antonio Simões, Sophie Françoise Mauricette Derchain / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-09T07:56:09Z (GMT). No. of bitstreams: 1 Campos_ElisabeteAparecida_M.pdf: 376476 bytes, checksum: 5cb1313dd5ebc4ab5d963f22dad4830d (MD5) Previous issue date: 2007 / Resumo: Objetivo: Avaliar a recuperação e estabilidade do DNA para detecção do papillomavírus humano (HPV) através da Reação em Cadeia da Polimerase (PCR) utilizando amostras estocadas por até 24 meses em Universal Collection Medium (UCM) com reagente desnaturante. Métodos: Sessenta amostras de citologia da cérvix uterina positivas para HPV, - que foram coletadas em UCM com resultado de Papanicolaou NIC 2 e NIC 3 entre os anos de 2003 e 2005 e que foram estocadas - foram utilizadas para este estudo. Todas as amostras haviam sido congeladas a ¿20°C após a adição do reagente desnaturante (0,05% de azida sódica + solução de NaOH) e da retirada da alíquota necessária para a realização do teste de Captura¿Híbrida 2 (CH 2) para identificação do DNA-HPV. O tempo de estocagem das amostras utilizadas foi de 6, 12 e 24 meses (20 amostras para cada tempo de estocagem). A extração do DNA foi realizada de acordo com protocolo específico para este tipo de material. A técnica de PCR foi realizada para confirmação da presença e da integridade do DNA através da detecção da ß-globina humana utilizando-se primers de consenso G73 e G74, e a detecção do DNA-HPV foi realizada utilizando-se os primers de consenso PGMY09 e PGMY11. Resultados: O DNA extraído do material desnaturado foi recuperado em 57 das 60 (95%) amostras estudadas. O DNA-HPV só não pôde ser detectado por PCR em uma destas amostras recuperadas. Conclusão: A recuperação e a estabilidade do DNA-HPV foi excelente após dois anos de estocagem do material cervical colhido em UCM com reagente desnaturan / Abstract: Objective: To evaluate the recovery and stability of DNA for the detection of HPV by Polymerase Chain Reaction (PCR) from clinical specimens stored for up to 24 months in Universal Collection Medium (UCM) with denatured reagent. Materials and methods: Sixty stores HPV-positive cervical smears collected from women with CIN 2 or CIN 3 diagnosis at Pap smear cytology between 2003 and 2005 were utilized to study. All samples were stored at ¿20°C after add of the denaturing reagent (sódica azida 0,05% and solution NaOH) and removing the aliquot required for carrying out the hybrid capture 2 assay for the identification of HPV-DNA, the samples were stored for 6, 12 or 24 months (20 samples for each storage time). DNA-HPV extraction was performed according to a protocol specifically designed for this type of material. The presence and quality of DNA was confirmed by human ß-globin detection using the consensus primers G73 and G74 and HPV was detected using the consensus primers PGMY09 and PGMY11 through the technique of PCR. Results: The DNA extracted from the denatured material was recovered in 57 out of 60 (95%) of the samples studied. DNA-HPV failed to be detected in one of the recovered samples. Conclusions: The recovery and stability of DNA-HPV from cervical samples stored for up to two years in UCM were excellent / Mestrado / Ciencias Biomedicas / Mestre em Tocoginecologia

Orientador: Maria Helena Baena de Moraes Lopes, Luiz Carlos Zeferino / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-11T17:49:00Z (GMT). No. of bitstreams: 1 Lopes_ErikaSimone_M.pdf: 700074 bytes, checksum: 3a0807c77000f2ca7cc189faee445613 (MD5) Previous issue date: 2007 / Resumo: O presente estudo visou descrever o processo atual de produção, distribuição e uso do fixador nas Unidades Básicas Saúde (UBSs), de Campinas, SP, os recursos humanos e materiais disponíveis para a coleta de exame citopatológico, bem como a técnica de fixação utilizada e comparar a adequabilidade dos esfregaços citopatológicos coletados nas UBSs utilizando diferentes técnicas de fixação. Foi desenvolvido um estudo descritivo, comparativo e prospectivo. Foram incluídos 2.114 esfregaços citopatológicos coletados em 43 UBSs, nas quais foram observadas informações sobre condições do espaço físico, armazenamento do fixador, técnicas de fixação dos esfregaços citopatológicos utilizadas, os profissionais responsáveis pela coleta e o processo atual de produção, distribuição e uso do fixador nas UBSs. A distribuição do fixador para as UBS foi de acordo com três tipos de técnicas de fixação: gotas, spray e álcool. Em 93% das UBSs os fixadores são armazenados em armário, já em 60,5% os rótulos com a data de fabricação não estava presente. A técnica de fixação mais utilizada foi gotas (93%), e a agitação do frasco era realizada em 86% das UBSs. A incidência de luz sobre o fixador foi observada em 90,6% das UBS. As trocas dos fixadores ocorrem em 46,5% semanalmente e em 81,4 % observou-se que os frascos encontravam-se fechados nas UBSs. Os profissionais que realizam os exames são 86% auxiliares de enfermagem, 84% por médicos, e em 51% por enfermeiras. Sessenta e cinco por cento das UBS apresentaram ventilador na sala de coleta, e 97,6% a presença de janela, e destas 73,8% encontravam-se abertas durante o procedimento de coleta. As freqüências de resultados ¿satisfatórios, mas limitados por fixação¿ variam de 14,9 a 23,2%, sendo significativamente mais baixa quando se usa o fixador na apresentação em spray (p<0,0001). A freqüência de resultados ¿satisfatórios, mas limitados por ausência de células glandulares e metaplásicas¿ com os diferentes tipos de fixadores variou de 13,8 a 22,3%, com menores taxas quando se usa o spray (p=0,0001). Não houve diferença significativa em relação à freqüência de lesões de baixo e alto grau, comparando-se os diferentes tipos de fixação. Quando se fez a fixação com álcool a 95% observou-se freqüência mais elevada do diagnóstico ASC-US, (p= 0,0025). A produção do fixador celular preparado pelo Laboratório de Citopatologia do CAISM para ser utilizado nas UBSs e o ambiente físico observado está dentro das normas e dos padrões descritos na literatura. Já o uso do fixador precisa ser revisto, observando-se as trocas, data de validade, manutenção do frasco fechado e em local protegido do calor. Na maioria das UBSs visitadas os profissionais pela coleta são auxiliares de enfermagem ou médicos que utilizam a técnica de fixação em gotas. A técnica de fixação que apresentou melhor desempenho foi polietilenoglicol e álcool em apresentação spray. Esta poderá ser uma alternativa mais adequada para ser implantada na rotina de coleta do exame citopatológico. A técnica de fixação em álcool a 95% elevou a identificação de ASC-US, o que necessita de melhor avaliação e análise. Os esfregaços nos quais se utilizou a técnica de fixação polietilenoglicol e álcool 95% em spray e álcool a 95% apresentaram menor freqüência de resultados satisfatórios, mas limitados por ausência de células glandulares ou metaplásicas. Este achado também carece de melhor investigação. Palavras-chave: esfregaço vaginal, neoplasia do colo uterino, controle de qualidade, citologia, fixadores / Abstract: To describe the current process of production, distribution and use of the fixative in the Basic Health Units (BHU), from Campinas, SP, the human resources and available materials to the smear test collection as well as the used fixation techniques, and to compare the quality of the Pap smears collected in the BHU, by using the different fixation techniques. It was developed a descriptive, comparative and prospective study. The sample was of 2114 Pap smears in 43 BHU, in which were observed information about the physical space conditions, manner of storage of the fixative, fixation techniques of the used Pap smears, the professional responsible for the collect, and the current process of production, distribution and use of the fixative in the BHU. The distribution of the fixative to the BHU was divided into three groups, with three types of fixation: drops, spray and alcohol. The smears were analyzed in the Cytopathology Laboratory from CAISM in the State University in Campinas. In 93% of the BHU, the fixatives are stored in cabinets, and in 60,5% of the labels there was no fabrication date. The most used fixation technique was drops (93%) and the flask shake was performed in 86% of the BHU. The light incidence on the fixative was observed in 90,6%. The fixative change occurs in 46,5% weekly and in 81,4% it was observed that the flasks were found closed in the BHU. The exams are performed in the BHU by 86% nurse auxiliary, 84% by physicians, and in 51% by nurses. In physical environment, it was observed that 65% of the BHU had ventilators in the collect room, in 97,6% there were windows and from these, in 73,8%, the windows were opened during the collect procedure. The frequencies of results ¿satisfactory, but limited by fixation¿ vary between 14,9% to 23,2%, being significantly lower when the spray fixative is used (p<0,0001). The frequency of results ¿satisfactory, but limited by the absence of glandular and metaplasic cells¿, with different types of fixatives, varied from 13,8% to 22,3%, with lower taxes when the spray is used (p=0,0001). There was no significant difference in relation to the lesions of low and high grades, comparing the different fixation types. When alcohol in 95% fixation was done, it was observed a higher frequency of the ASCUS diagnosis (p=0,0025). The production of the cellular fixative is inside the patterns described in literature. The fixative use must be reviewed, observing the changes, validity date, maintenance of the flask (closed and in a heat-protected place). In most of the visited BHU, the professional responsible for the collect are nurse auxiliaries or physicians that use the drop fixation. The physical environment is according to the norms described in literature. The fixation technique that presented the best performance was spray. This can be a more adequate alternative to be implanted in the routine of the Pap smear collect. The alcohol in 95% fixation raised the ASC-US identification, which needs better evaluation and analysis. The Pap smears in which the fixation technique polyethylene glycol and alcohol 95% in spray and alcohol in 95% was used, presented lower frequency of satisfactory results, but limited by the absence of glandular and metaplasic cells. This findind also needs better investigation. Key words: Vaginal smears, Uterine Cervical Neoplasm, Quality control, Cytology, Fixatives / Mestrado / Enfermagem e Trabalho / Mestre em Enfermagem

Made available in DSpace on 2014-12-17T14:46:55Z (GMT). No. of bitstreams: 1 MagnaMPS_DISSERT.pdf: 1336445 bytes, checksum: 2998e1c0551bf591c5ce1acc115c4190 (MD5) Previous issue date: 2011-11-18 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / A quantitative, descriptive, cross-sectional and retrospective study, using technical procedures of document consultation from secondary sources and health household survey with application form for face to face inter views, with the assent n?.039/2011 from the Ethics Committee of the Federal University of Rio Grande do Norte. The aim of this study was to analyze the cervix cancer control in the area47 of the Health Family Centre Nova Natal II. The cancer cervix is the second most common cancer among women worldwide. In Brazil screening for early detection and treatment of disease has been poorly done and follow-up to reduce mortality has not been executed. From a total of1170women belonging to area 47, who under went screening by the Pap test in the period from 2005 to 2010,was elected a sample of 38 women with positive cervical changes, over 18 years old. The calculation of frequency analysis of socio demographic and clinical and epidemiological selected variables with the results of cervical changes, using the X2 test and taking as significance level of p<0.05 was not statistically significant. The predominant age range was 25 to 64 years (68.9%), most no white women (60.5%), predominantly with primary education (57.9%), most married (68.4%) and housewives (68.4%) with early age of sexual activity (86.8%), the minority smokers (13.2%), with a sexual partner (36.8%). At the time of interview, 42.1% of the women voiced complaint of discharge, while only 2.6% reported bleeding. In relation to the occurrence of STDs (including HPV), 10.5% of women reported being a carrier. The use of oral contraceptives was 32.3% of women, from 2 to 4 years (44.4%). The result of the last screening test performed, showed prevalence of immature squamous metaplasia (55.3%), followed by intraepithelial low- grade lesion (including the cytopathologic HPV effect and cervical intra epithelial neoplasia grade I) (31.6%); intraepithelial high-grade lesion (including cervical intraepithelial neoplasia grade II and III) (7.9%), atypical squamous non neoplastic cells (5.3%). There was no squamous cell carcinoma and adenocarcinoma. Most women received information about the action that should be done after the last screening test result (55.3%), but how to perform follow, most women did not report having done so (55.3%). The follow-up group of women studied, with varying degrees of cervical abnormalities, should only be completed with the discharge by cure, established inconsecutive negative cytology, a goal that is not being achieved in the area 47 of the Health Family Centre of Nova Natal II / Estudo quantitativo realizado por meio de pesquisa descritiva, transversal e retrospectiva, utilizando procedimentos t?cnicos de consulta documental a fontes secund?rias e inqu?rito domiciliar com aplica??o de formul?rio de entrevistas face a face, ap?s parecer favor?vel n? 039/2011 do Comit? de ?tica em Pesquisa da Universidade Federal do Rio Grande do Norte. O objetivo dessa pesquisa foi analisar a resolutividade do controle da neoplasia maligna do colo de ?tero na ?rea 47 da Unidade de Sa?de da Fam?lia Nova Natal II. A neoplasia maligna do colo de ?tero ? o segundo tipo de c?ncer mais frequente entre as mulheres no mundo. No Brasil o rastreamento para detec??o e tratamento precoces da doen?a tem sido efetuado precariamente e o seguimento, para reduzir a mortalidade, n?o tem sido executado. De um total de 1170 mulheres pertencentes ? ?rea 47, que se submeteram a rastreamento por meio do exame de Papanicolau, no per?odo de 2005 a 2010, elegeu-se uma amostra de 38 mulheres com resultado positivo de altera??es cervicais, maiores de 18 anos. A an?lise do c?lculo da frequ?ncia de vari?veis sociodemogr?ficas e cl?nico-epidemiol?gicas selecionadas com os resultados das altera??es cervicais, utilizando-se o teste de X2 e adotando como n?vel de signific?ncia p<0,05 n?o mostrou signific?ncia estat?stica. A faixa et?ria predominante foi de 25 a 64 anos (68,9%); a maioria parda (60,5%); com escolaridade predominante at? o ensino fundamental (57,9%); a maioria casada ou em conviv?ncia marital (68,4%) e donas de casa (68,4%); com in?cio precoce da atividade sexual (86,8%), a minoria fumante (13,2%), com um parceiro sexual (36,8%). No momento da entrevista, 42,1% das mulheres verbalizou queixa de corrimento, enquanto apenas 2,6% referiu sangramento. Em rela??o ? ocorr?ncia de DSTs (inclusive HPV), 10,5% das mulheres declarou ser portadora. Verbalizaram o uso de contraceptivos orais, 32,3% das mulheres, por 2 a 4 anos (44,4%). Quanto ao resultado do ?ltimo exame preventivo realizado, prevaleceu a metaplasia escamosa imatura (55,3%), seguido de les?o intraepitelial de baixo grau (compreendendo efeito citopatol?gico pelo HPV e neoplasia intra-epitelial cervical grau I) (31,6%); les?o intra-epitelial de alto grau (compreendendo neoplasias intra-epiteliais cervicais de grau II e III) (7,9%); c?lulas at?picas escamosas de significado indeterminado, possivelmente n?o neopl?sicas, (5,3%). N?o foi observado carcinoma de c?lulas escamosas e adenocarcinoma. A maioria das mulheres recebeu informa??es sobre o seguimento que deveria ser realizado ap?s o resultado do ?ltimo exame preventivo (55,3%), mas, quanto a realizar o seguimento, a maior parte das mulheres n?o referiu t?-lo feito (55,3%). O seguimento do grupo de mulheres analisadas, com diferentes graus de altera??es cervicais, somente deveria ser finalizado com a alta por cura, estabelecido em citologias consecutivas negativas, meta que n?o est? sendo atingida na ?rea 47 da Unidade de Sa?de da Fam?lia Nova Natal II