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University of Technology Sydney. Faculty of Health. Vaccination programs can provide an effective means to control infectious diseases at a population level. Evaluating the impact of these programs after implementation can be complicated by limitations of routine surveillance systems and lack of routine testing to confirm diagnosis, as well as natural fluctuations in disease rates over time. This thesis provides a structured explanation of statistical methods and how they can be used to address the epidemiological challenges in assessing changes in burden of disease as a result of vaccination programs. It explores statistical approaches to the evaluation of vaccination programs at a population level, using rotavirus vaccination in New South Wales (NSW), Australia, as a case study. A summary of the key features that need to be considered when trying to detect any changes in the burden of infectious diseases due to vaccination is given. An assessment of the impact of the Australian rotavirus vaccination program, introduced in 2007, on hospitalisations and emergency department (ED) presentations of children aged under five years for all-cause gastroenteritis in NSW from July 2001 to June 2013 was conducted. Previously published methods that separate these hospitalisations and ED presentations into those due to rotavirus and those that are not are compared. A simulation study is used to explore these methods in controlled scenarios to determine the most appropriate method for these data. The Australian rotavirus vaccination program had an almost immediate impact and led to a fifty and sixteen percent reduction in the rate of hospitalisations and ED presentations for acute gastroenteritis within the first 2.5 years. These declines were mostly attributed to a decline in the size of the seasonal peak. The methods to determine rotavirus cases from all-cause gastroenteritis cases had different strengths and limitations and the derived estimates varied. No robust method was identified from the simulation study for our data. Each method that relied on using weekly counts of positive rotavirus laboratory tests to estimate rotavirus-attributable cases underestimated the true number of rotavirus cases when their assumptions held. The evaluation of the effectiveness of vaccination programs requires the use of rigorous statistical methods to ensure the robustness and validity of findings. Appropriate statistical methods that account for temporal trends are needed to provide a detailed understanding of any changes in disease burden observed. While this thesis focused on rotavirus disease burden in NSW, Australia, many of the concepts discussed are applicable to other infectious diseases.

FUNDAMENTO: En nuestro país existen dos tipos de vacunas disponibles frente a la parotiditis infecciosa. En los últimos tiempos se han planteado dudas sobre la eficacia global de estas vacunas y de la eficacia comparada entre ambas (cepa Rubini y cepa Jeryl Lynn). En el distrito sanitario de A.P. "Sevilla Este" se registraron 256 casos durante 1997 (90,1 casos por 100.000 habitantes). Con este estudio se pretende aprovechar la aparición de casos de parotiditis para evaluar poblaciones afectadas e incidencia comparada según tipo de vacuna recibida durante la infancia. MÉTODOS: Análisis descriptivo de los casos (edad, distribución territorial, antecedentes vacunales,...) y análisis evolutivo (tasas de incidencia anuales) en el distrito sanitario y su entorno. Se evalúa la efectividad global de las vacunas frente a la parotiditis. Igualmente se estiman las tasas de incidencia de casos entre los vacunados con cepa Rubini y Jeryl Lynn. RESULTADOS: Se observan las tasas de incidencias más elevadas en niños entre 1 y 4 años. Se han estimado niveles de efectividad global para estas vacunas. Además se observa una incidencia de casos significativamente más elevada entre los niños vacunados con cepa Rubini que en los que lo hicieron con Jeryl Lynn (riesgo relativo de 6,5 con Intervalo de confianza 95% 3,6-11,8). CONCLUSIONES: La efectividad que se desprende de este estudio no parece ser tan buena como la eficacia teórica preconizada para las vacunas frente a la parotiditis. Se plantea la conveniencia de realizar otros estudios de casos según tipos de vacunas utilizadas. Igualmente son de gran interés los datos a suministrar por estudios seroepidemiológicos. BACKGROUND: In our country, there are two types of infectious mumps vaccines available. In recent times, doubts have been raised regarding the overall effectiveness of these vaccines and the comparative effectiveness of the two strains (Rubini strain and Jeryl Lynn strain). In the "East Seville" Primary Care district, 245 cases were reported in 1997 (90.1 cases per 100,000 inhabitants). This study is aimed at taking advantage of the outbreak of cases of mumps to evaluate affected populations and comparative incidence according to type of vaccines given during childhood. METHODS: Descriptive analysis of the cases (age, territorial spread, inoculation history…) and trend analysis (annual incident rates) within this health care district and the surrounding area. The overall effectiveness of the mumps vaccines. The case incidence rates among those inoculated with Rubini strain and those inoculated with Jeryl Lynn strain are also estimated. RESULTS: The highest rates of incidence are found among children in the 1-4 age range. Overall effectiveness rates for these vaccines have been estimated. A significantly higher rate of infection has been found among the children inoculated with Rubini strain than those inoculated with the Jeryl Lynn strain (relative risk of 6.5 with a Confidence Interval of 95% 3.6-11.8). CONCLUSIONS: The effectiveness which follows from this study does not seem as good as the theoretical effectiveness anticipated for the mumps vaccines. It thus seems advisable for other case studies to be conducted by types of vaccines used. The data to be furnished by means of sero-epidemiological studies are also of major interest.

BACKGROUND: This report is a systematic review of the effect intensity and duration of the immune response to meningococcal serogroup C vaccine. The vaccine safety, efficacy and effectiveness are also analyzed. METHODS: MEDLINE literature search in the period 1970-1996. Meningoccocal polysaccharide vaccine clinical trials and human prospective studies were specifically searched. Quality of the retrieved studies were analyzed. Information available was integrated. RESULTS: Group C meningoccal polysaccharide vaccine is a safe product. Its efficacy is over 85% among adults and children over 5 years old. 70% (CI 95%: 5-91%) under 5 years old, and 55% among children 2-3 years old. The vaccine is not effective under 2 years. The duration of protective antibody levels decrease with age. The proportion of vaccinated children effectively protected one year after vaccination is low. Vaccination does not affect the immune response to ulterior revaccination. CONCLUSIONS: Group C meningococcal polysaccharide vaccine is indicated in adults and children over 2 years old to protect them from meningococcal disease due to group C when exposed to high risk of infection. The outbreaks control is the main indication for the use of this vaccine. Routine immunization in not outbreak situation is not recommended due to the small vaccine protection in children under 2 years old, the limited efficacy in children under 5, and the short duration of the immunity in children. Fundamento: Este trabajo consiste esencialmente en una revisión sistemática de la literatura científica sobre los efectos, intensidad y duración de la respuesta serológica, así como sobre la eficacia, efectividad y seguridad de la vacuna meningocócica de polisacárido capsular del grupo C. Métodos: Búsqueda en repertorio MEDLINE en el periodo 1970-1996. Búsqueda específica de ensayos clínicos aleatorizados y estudios de intervención prospectivos en humanos con vacunas de polisacáridos capsulares de meningococo en el mismo repertorio y periodo. Análisis crítico de literatura científica y síntesis de evidencia. Resultados: La vacuna de polisacárido capsular del serogrupo C es considerada segura y ha mostrado una eficacia superior al 85% en adultos y niños mayores, 70% (IC95%: 5-91%) en niños menores de 5 años y 55% (IC90%: 14-76%) en niños de 2-3 años. La vacuna no se ha mostrado eficaz en niños menores de 2 años. La duración de niveles de anticuerpos protectores disminuye con la edad. La proporción de niños menores de 6 años efectivamente protegidos al año de la vacunación es baja. La vacunación no limita la respuesta serológica de vacunaciones ulteriores. Conclusiones: La vacuna meningocócica de polisacárido capsular del serogrupo C está indicada en adultos y niños mayores de 2 años como protección contra la enfermedad meningocócica causada por este serogrupo en situaciones de alto riesgo de enfermedad. La escasa protección que ofrece la vacuna en los menores de 2 años, la limitada eficacia en menores de 5 años y la corta duración de la inmunidad que confiere a estas edades, hace que la vacunación rutinaria no esté recomendada y que la vacuna se use fundamentalmente en el control de brotes epidémicos causados por serogrupo C.