Randomized, double-blinded, controlled non-inferiority trials evaluating the immunogenicity and safety of fractional doses of Yellow Fever vaccines in Kenya and Uganda.

Introduction: Yellow fever is endemic in specific regions of sub-Saharan Africa and the Americas, with recent epidemics occurring on both continents. The yellow fever vaccine is effective, affordable and safe, providing life-long immunity following a single dose vaccination. However, the vaccine production process is slow and cannot be readily scaled up during epidemics. This has led the World Health Organization (WHO) to recommend the use of fractional doses as a dose-sparing strategy during epidemics, but there are no randomized controlled trials of fractional yellow fever vaccine doses in Africa. Methods and analysis: We will recruit healthy adult volunteers, adults living with HIV, and children to a series of randomized controlled trials aiming to determine the immunogenicity and safety of fractional vaccine doses in comparison to the standard vaccine dose. The trials will be conducted across two sites; Kilifi, Kenya and Mbarara, Uganda. Recruited participants will be randomized to receive fractional or standard doses of yellow fever vaccine. Scheduled visits will include blood collection for serum and peripheral blood mononuclear cells (PBMCs) before vaccination and on various days - up to 2 years - post-vaccination. The primary outcome is the rate of seroconversion as measured by the plaque reduction neutralization test (PRNT 50) at 28 days post-vaccination. Secondary outcomes include antibody titre changes, longevity of the immune response, safety assessment using clinical data, the nature and magnitude of the cellular immune response and post-vaccination control of viremia by vaccine dose. Ethics and dissemination: The clinical trial protocols have received approval from the relevant institutional ethics and regulatory review committees in Kenya and Uganda, and the WHO Ethics Review Committee. The research findings will be disseminated through open-access publications and presented at relevant conferences and workshops. Registration: ClinicalTrials.gov NCT02991495 (registered on 13 December 2016) and NCT04059471 (registered on 15 August 2019).

Costes directos de la diabetes mellitus y de sus complicaciones en España (Estudio SECCAID: Spain estimated cost Ciberdem-Cabimer in Diabetes) / Direct cost of diabetes mellitus and its complications in Spain (SECCAID Study: Spain estimated cost Ciberdem-Cabimer in Diabetes)

OBJETIVO: Estimar los costes directos generados por la diabetes mellitus (DM), tanto tipo 1 como tipo 2, desde la perspectiva del Sistema Nacional de Salud. MATERIAL Y MÉTODO: Estudio del coste de la enfermedad mediante un enfoque de prevalencia, a través del análisis y la revisión de las bases de datos y de la literatura relacionada con el uso de recursos en la DM. Las categorías de costes directos anuales considerados fueron: hospitalarios (incluyendo la atención ambulatoria), atención primaria (incluyendo pruebas complementarias y tiras reactivas de automonitorización de glucemia capilar) y, fármacos. Para los costes no relacionados, solo se incorporó el sobrecoste. Adicionalmente, se analizó el coste de las complicaciones independientemente de la categoría de costes donde se hubieran originado. Todos los costes fueron actualizados a euros de 2012. RESULTADOS: El coste directo total anual de la DM ascendió a 5.809 millones de euros, que representó el 8,2% del gasto sanitario total. Los costes farmacológicos fueron la categoría con mayor peso sobre el coste directo total (38%), seguido por los costes hospitalarios (33%). El coste farmacológico fue de 2.232 millones de euros, donde los fármacos antidiabéticos aportaron 861 millones de euros (15%). Las tiras reactivas de automonitorización de glucemia capilar contribuyeron en 118 millones de euros (2%). El coste total de complicaciones en general fue de 2.143 millones de euros. CONCLUSIONES: Los costes de la DM representan una proporción muy elevada del total del gasto sanitario español, siendo imprescindible introducir estrategias y medidas para mejorar la eficiencia en el control y el tratamiento de la DM para reducir así sus complicaciones y los enormes costes humanos y económicos asociados a la enfermedad

OBJECTIVE: The aim of the study was to estimate the direct costs associated with type 1 and 2 diabetes mellitus in Spain taking into account a National Health Service perspective. METHOD: A costs of illness study was conducted using the prevalence approach and data from existing databases and bibliographic references related to the use of resources in the treatment of diabetes mellitus. The costs categories analysed were: hospital costs (including outpatient care), primary care costs (including additional tests cost and self monitoring blood glucose strips cost) and drug costs. In calculating the non-related cost, only the extra cost was taken into account. Additionally, we analysed the complications cost independently of where costs were originated. Costs were updated to 2012 euros. RESULTS: The total direct annual cost of diabetes mellitus was 5,809 million euros, representing 8.2% of the total Spanish health expenditure. Drug costs was the major component of total cost (38%), followed by hospital costs (33%). Drug costs accounted for 2,232 million euros, with antidiabetic drugs costs being 861 million euros (15%). Self monitoring blood glucose strips only contributed 118 million euros (2%) to the total cost. The cost of complications cost was 2,143 million euros, around 37% of the total. CONCLUSIONS: Total direct costs associated with diabetes mellitus represent a high proportion of total Spanish health expenditure. It is crucial to introduce measures and strategies to improve efficiency in the control and treatment of diabetes mellitus, with the final purpose of reducing its complications and the considerable economic impact generated