WHO policy development processes for a new vaccine: case study of malaria vaccines

<p>Abstract</p> <p>Background</p> <p>Recommendations from the World Health Organization (WHO) are crucial to inform developing country decisions to use, or not, a new intervention. This article analysed the WHO policy development process to predict its course for a malaria vaccine.</p> <p>Methods</p> <p>The decision-making processes for one malaria intervention and four vaccines were classified through (1) consultations with staff and expert advisors to WHO's Global Malaria Programme (GMP) and Immunization, Vaccines and Biologicals Department (IVB); (2) analysis of the procedures and recommendations of the major policy-making bodies of these groups; (3) interviews with staff of partnerships working toward new vaccine availability; and (4) review and analyses of evidence informing key policy decisions.</p> <p>Case description</p> <p>WHO policy formulation related to use of intermittent preventive treatment in infancy (IPTi) and the following vaccine interventions: <it>Haemophilus influenzae </it>type b conjugate vaccine (Hib), pneumococcal conjugate vaccine (PCV), rotavirus vaccine (RV), and human papillomavirus vaccine (HPV), five interventions which had relatively recently been through systematic WHO policy development processes as currently constituted, was analysed. Required information was categorized in three areas defined by a recent WHO publication on development of guidelines: safety and efficacy in relevant populations, implications for costs and population health, and localization of data to specific epidemiological situations.</p> <p>Discussion and evaluation</p> <p>Data needs for a malaria vaccine include safety; the demonstration of efficacy in a range of epidemiological settings in the context of other malaria prevention interventions; and information on potential rebound in which disease increases subsequent to the intervention. In addition, a malaria vaccine would require attention to additional factors, such as costs and cost-effectiveness, supply and demand, impact of use on other interventions, and distribution issues.</p> <p>Conclusions</p> <p>Although policy issues may be more complex for future vaccines, the lead-time between the date of product regulatory approval and a recommendation for its use in developing countries is decreasing. This study presents approaches to define in advance core data needs to support evidence-based decisions, to further decrease this lead-time, accelerating the availability of a malaria vaccine. Specific policy areas for which information should be collected are defined, including studying its use within the context of other malaria interventions.</p

Modeling the public health impact of malaria vaccines for developers and policymakers

Efforts to develop malaria vaccines show promise. Mathematical model-based estimates of the potential demand, public health impact, and cost and financing requirements can be used to inform investment and adoption decisions by vaccine developers and policymakers on the use of malaria vaccines as complements to existing interventions. However, the complexity of such models may make their outputs inaccessible to non-modeling specialists. This paper describes a Malaria Vaccine Model (MVM) developed to address the specific needs of developers and policymakers, who need to access sophisticated modeling results and to test various scenarios in a user-friendly interface. The model's functionality is demonstrated through a hypothetical vaccine.; The MVM has three modules: supply and demand forecast; public health impact; and implementation cost and financing requirements. These modules include pre-entered reference data and also allow for user-defined inputs. The model includes an integrated sensitivity analysis function. Model functionality was demonstrated by estimating the public health impact of a hypothetical pre-erythrocytic malaria vaccine with 85% efficacy against uncomplicated disease and a vaccine efficacy decay rate of four years, based on internationally-established targets. Demand for this hypothetical vaccine was estimated based on historical vaccine implementation rates for routine infant immunization in 40 African countries over a 10-year period. Assumed purchase price was $5 per dose and injection equipment and delivery costs were$0.40 per dose.; The model projects the number of doses needed, uncomplicated and severe cases averted, deaths and disability-adjusted life years (DALYs) averted, and cost to avert each. In the demonstration scenario, based on a projected demand of 532 million doses, the MVM estimated that 150 million uncomplicated cases of malaria and 1.1 million deaths would be averted over 10 years. This is equivalent to 943 uncomplicate cases and 7 deaths averted per 1,000 vaccinees. In discounted 2011 US dollars, this represents $11 per uncomplicated case averted and$1,482 per death averted. If vaccine efficacy were reduced to 75%, the estimated uncomplicated cases and deaths averted over 10 years would decrease by 14% and 19%, respectively.; The MVM can provide valuable information to assist decision-making by vaccine developers and policymakers, information which will be refined and strengthened as field studies progress allowing further validation of modeling assumptions

Escuelas limpias: proyecto de gestión ambiental

Environmental problems, pollution and global warming can be addressed from different perspectives. This project seeks to be an effective proposal to address these issues. It directs its efforts to the development of a process of awareness of young Peruvians between the ages of 11 and 15, to be incorporated into public schools through a program of environmental education. It starts from identifying a district model with critical levels of pollution in which to promote and implement an appropriate environmental education to contribute to the improvement and welfare of the environment The Independencia district was selected for it shows acute health problems, pollution and poor environmental awareness and culture, with the whole purpose of changing the attitude of a group of young people, parents and teachers to the social and environmental problems of their environment, instilling in them awareness and training in environmental education to create a multiplier effect and to improve their quality of life.Los problemas del medio ambiente, su contaminación y el calentamiento global pueden ser abordados desde diferentes perspectivas. Este proyecto busca ser una propuesta eficaz para enfrentarlos. Destina sus esfuerzos al desarrollo de un proceso de concientización de los jóvenes peruanos entre los 11 y los 15 años, para ser incorporado en las instituciones educativas públicas a través de un programa de gestión ambiental escolar. Parte de determinar un distrito modelo con niveles críticos de contaminación en el cual promover y aplicar una adecuada educación ambiental que contribuya al mejoramiento y el bienestar del entorno. Se seleccionó el distrito de Independencia, el cual muestra agudos problemas de salud, contaminación y escasa conciencia y cultura ambiental, con el propósito de cambiar la actitud de un grupo de jóvenes, padres y profesores ante la problemática social y ambiental de su entorno, inculcando en ellos conciencia y formación en educación ambiental para poder crear un efecto multiplicador y mejorar su calidad de vida

Periodic fever in pediatrics : ambulatory approach.

Revista Ciencias Biomédicas Vol.9, Núm.1 (2020) Pag. 44 - 53La fiebre es un síntoma frecuente en la edad pediátrica; la mayoría de las veces es causada por infecciones de etiología viral que se autolimitan. En raras ocasiones los pacientes pueden cursar con episodios de fiebre de días a semanas de duración asociados a síntomas específicos, que se encuentran separados por intervalos asintomáticos, con una periodicidad predecible (fiebre periódica). En estos pacientes es importante realizar una historia clínica completa, con un interrogatorio y examen físico detallados, excluir las causas infecciosas más frecuentes y posteriormente realizar exámenes de laboratorio que permitan establecer un diagnóstico sindromático. El objetivo del presente artículo es describir el abordaje diagnóstico de los pacientes pediátricos con síndromes de fiebre periódica desde el ámbito ambulatorio

Propuesta estratégica de mejora en la implementación de los estándares mínimos del Sistema de Gestión de la Seguridad y Salud en el Trabajo (SG-SST) en la empresa Bancamia S.A sede Chía para el segundo semestre del 2019 y principios del 2020.

Matriz de evaluación del Sistema de Gestión en Seguridad y Salud en el trabajoPropuesta estratégica de mejora en la implementación de los estándares mínimos del sistema de gestión de la seguridad y salud en el trabajo (sg-sst) en la empresa bancamia s.a sede chía para el segundo semestre del 2019 y principios del 2020.Strategic proposal to improve the implementation of the minimum standards of the management system of occupational safety and health (sg-sst) in the company bancamia s.a headquarters for the second half of 2019 and the beginning of 2020

Carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-haematopoietic stem cell transplant: a retrospective cohort study

Background Risk factors for carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-HSCT have not been thoroughly explored. Methods All children with cancer or post-HSCT who developed Enterobacterales bloodstream infections in two cancer referral centres in major Colombian cities between 2012 and 2021 were retrospectively examined. When the infection episode occurred, carbapenem resistance mechanisms were evaluated according to the available methods. Data were divided in a training set (80%) and a test set (20%). Three internally validated carbapenem-resistant Enterobacterales (CRE) prediction models were created: a multivariate logistic regression model, and two data mining techniques. Model performances were evaluated by calculating the average of the AUC, sensitivity, specificity and predictive values. Results A total of 285 Enterobacterales bloodstream infection episodes (229 carbapenem susceptible and 56 carbapenem resistant) occurred [median (IQR) age, 9 (3.5–14) years; 57% male]. The risk of CRE was 2.1 times higher when the infection was caused by Klebsiella spp. and 5.8 times higher when a carbapenem had been used for ≥3 days in the previous month. A model including these two predictive variables had a discriminatory performance of 77% in predicting carbapenem resistance. The model had a specificity of 97% and a negative predictive value of 81%, with low sensitivity and positive predictive value. Conclusions Even in settings with high CRE prevalence, these two variables can help early identification of patients in whom CRE-active agents are unnecessary and highlight the importance of strengthening antibiotic stewardship strategies directed at preventing carbapenem overuse.Q1Q1Los factores de riesgo de resistencia a los carbapenémicos en las infecciones del torrente sanguíneo por Enterobacterales entre niños con cáncer o después de un TCMH no se han explorado a fondo. Métodos Se examinaron retrospectivamente todos los niños con cáncer o post-TCMH que desarrollaron infecciones del torrente sanguíneo por Enterobacterales en dos centros de referencia de cáncer en las principales ciudades de Colombia entre 2012 y 2021. Cuando ocurrió el episodio de infección, se evaluaron los mecanismos de resistencia a los carbapenémicos según los métodos disponibles. Los datos se dividieron en un conjunto de entrenamiento (80%) y un conjunto de prueba (20%). Se crearon tres modelos de predicción de Enterobacterales resistentes a carbapenémicos (CRE) validados internamente: un modelo de regresión logística multivariante y dos técnicas de minería de datos. El rendimiento del modelo se evaluó calculando el promedio del AUC, la sensibilidad, la especificidad y los valores predictivos. Resultados Se produjeron un total de 285 episodios de infección del torrente sanguíneo por Enterobacterales (229 susceptibles a carbapenémicos y 56 resistentes a carbapenémicos) [mediana de edad (RIQ), 9 (3,5 a 14) años; 57% hombres]. El riesgo de CRE fue 2,1 veces mayor cuando la infección fue causada por Klebsiella spp. y 5,8 veces mayor cuando se había utilizado un carbapenem durante ≥3 días en el mes anterior. Un modelo que incluía estas dos variables predictivas tuvo un rendimiento discriminatorio del 77% en la predicción de la resistencia a los carbapenémicos. El modelo tuvo una especificidad del 97% y un valor predictivo negativo del 81%, con baja sensibilidad y valor predictivo positivo. Conclusiones Incluso en entornos con una alta prevalencia de CRE, estas dos variables pueden ayudar a la identificación temprana de pacientes en quienes los agentes activos de CRE son innecesarios y resaltar la importancia de fortalecer las estrategias de administración de antibióticos dirigidas a prevenir el uso excesivo de carbapenémicos.N/AS

Safety and immunogenicity of Ad26.COV2.S in adults: A randomised, double-blind, placebo-controlled Phase 2a dose-finding study

BACKGROUND: A single dose of Ad26.COV2.S is well-tolerated and effective in preventing moderate-to-severe disease outcomes due to COVID-19. We evaluated the impact of dose level, number of doses, and dose interval on immunogenicity, reactogenicity, and safety of Ad26.COV2.S in adults. Anamnestic responses were also explored. METHODS: This randomised, double-blind, placebo-controlled, Phase 2a study was conducted in adults aged 18-55 years and ≥ 65 years (NCT04535453). Four dose levels (1.25 × 10 10, 2.5 × 10 10, 5 × 10 10, and 1 × 10 11 viral particles [vp], single and 2-dose schedules, and dose intervals of 56 and 84 days, were assessed. Four or 6 months post-primary vaccination, Ad26.COV2.S 1.25 × 10 10 vp was given to evaluate anamnestic responses. Humoral and cell-mediated immune responses were measured. Reactogenicity and safety were assessed in all participants. RESULTS: All Ad26.COV2.S schedules induced humoral responses with evidence of a dose response relationship. A single dose of Ad26.COV2.S (5 × 10 10 vp) induced antibody and cellular immune responses that persisted for up to at least 6 months. In the 2-dose regimens, antibody responses were higher than 1-dose regimens at comparable dose levels, and the magnitude of the immune response increased when the interval between doses was increased (84 days vs 56 days). Rapid, marked immune responses were observed in all groups after vaccine antigen exposure indicating immune memory. Durable immune responses were observed in all groups for up to at least 6 months post-antigen exposure. Strong and consistent correlations between neutralising and binding antibodies were observed CD4 + and CD8 + T cell responses were similar after all regimens. Reactogenicity within 7 days post-vaccination tended to be dose-related. CONCLUSION: The study supports the primary, single dose schedule with Ad26.COV2.S at 5 × 10 10 vp and homologous booster vaccination after a 6 month interval. Rapid and marked responses to vaccine antigen exposure indicate induction of immune memory by 1- and 2-dose primary vaccination

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Measuring Soil Colour to Estimate Soil Organic Carbon Using a Large-Scale Citizen Science-Based Approach

Rapid, low-cost methods for large-scale assessments of soil organic carbon (SOC) are essential for climate change mitigation. Our work explores the potential for citizen scientists to gather soil colour data as a cost-effective proxy of SOC instead of conventional lab analyses. The research took place during a 2-year period using topsoil data gathered by citizen scientists and scientists from urban parks in the UK and France. We evaluated the accuracy and consistency of colour identification by comparing “observed” Munsell soil colour estimates to “measured” colour derived from reflectance spectroscopy, and calibrated colour observations to ensure data robustness. Statistical relationships between carbon content obtained by loss on ignition (LOI) and (i) observed and (ii) measured soil colour were derived for SOC prediction using three colour components: hue, lightness, and chroma. Results demonstrate that although the spectrophotometer offers higher precision, there was a correlation between observed and measured colour for both scientists (R2 = 0.42; R2 = 0.26) and citizen scientists (R2 = 0.39; R2 = 0.19) for lightness and chroma, respectively. Foremost, a slightly stronger relationship was found for predicted SOC using the spectrophotometer (R2 = 0.69), and citizen scientists produced comparable results (R2 = 0.58), highlighting the potential of a large-scale citizen-based approach for SOC monitoring