ABSTRACT In the current context, information, knowledge and innovation are essential to society, the economy, and territorial and organizational development. It is for this reason that ever since the year 1995 Cuba has implemented a science, technology and innovation system to establish links between the scientific community, the business community and the government. A diagnostic study was conducted based on the scientific historical-logical and dialectical method with the purpose of becoming acquainted with the historical foundations of knowledge management and their relationship to the system of science, technology and innovation, as well as with the knowledge management capacities and limitations of structures from the Ministry of Science, Technology and the Environment in Pinar del Río. A questionnaire was applied to collect the data, and document analysis was performed which comprised the study of texts on the specialty and reports about the main lessons learned. Results show that these organizations do not manage to effectively transfer the information, knowledge and innovations available in the academic community to the business community. An action program is proposed which includes designing a knowledge management model, building networking capacities, renewing knowledge, articulating the social communication strategy so that it permits greater visibility, and fostering the development of the scientific potential in keeping with territorial priorities.

RESUMEN En un contexto actual, la información, el conocimiento y la innovación son factores indispensables para la sociedad, la economía y el desarrollo territorial y organizacional. Por tales razones, Cuba ha implementado desde el año 1995 un sistema de ciencia, tecnología e innovación con el propósito de lograr la vinculación entre la comunidad científica, la comunidad empresarial y el gobierno. Con la finalidad de identificar las capacidades y las limitaciones que tienen las estructuras del Ministerio de Ciencia, Tecnología y Medio Ambiente de Pinar del Río para gestionar el conocimiento, se realizó un diagnóstico utilizando el método científico histórico-lógico y el dialéctico para conocer los fundamentos históricos que existen sobre la gestión del conocimiento y su articulación en el sistema de ciencia, tecnología e innovación. Se aplicó un cuestionario para la recolección de los datos y el análisis documental que comprendió el estudio de textos de la especialidad y de las principales experiencias reportadas. Los principales resultados muestran que estas organizaciones no logran transferir con efectividad la información, el conocimiento y las innovaciones disponibles en la comunidad académica hacia la comunidad empresarial. Se propone un programa de acciones que contempla el diseño de un modelo de gestión del conocimiento, crear capacidades para el trabajo en red, renovar el conocimiento, articular la estrategia de comunicación social que permita una mayor visibilidad y fomentar el desarrollo del potencial científico en función de las prioridades del territorio.

INTRODUCTION Pneumococcal infections are a major cause of morbidity and mortality and are associated with considerable economic burden on health systems. To prevent pneumococcal infections, 7-valent conjugate vaccines have been available for over a decade; more recently, 10- and 13-valent conjugate vaccines have been formulated, which are more immunogenic than vaccines with capsular polysaccharides only. In Cuba, a new vaccine candidate has been developed, PCV7-TT, a conjugate of tetanus toxoid with antigens of seven of the serotypes of Streptococcus pneumoniae with highest circulation in Cuba and in the world: 1, 5, 6B, 14, 18C, 19F and 23F. OBJECTIVE Assess the safety of the vaccine candidate PCV7-TT in healthy adults and conduct a preliminary assessment of its immunogenicity. METHODS A phase I, double-blind clinical trial was performed at the National Toxicology Center in Havana, Cuba. Healthy male volunteers aged 18–35 years were randomly assigned to two groups: 20 received the vaccine candidate PCV7-TT and 20 the polyvalent antipneumococcal vaccine PNEUMO-23 used as control, each in a single intramuscular dose. To assess safety, the occurrence of adverse events was monitored for 30 days following inoculation. To explore immunogenicity, concentrations of serotype-specific antibodies was quantified before and 30 days after inoculation, as well titers of opsonophagocytic antibodies. (National Clinical Trial Registry RPCEC00000133) RESULTS Local adverse events were pain, redness, induration, increased sensitivity to touch, and warmth in the injection area. Pain was registered in 70% of individuals who received PCV7-TT and in 75% of those vaccinated with PNEUMO-23. Reported systemic adverse events were general malaise, headache and drowsiness. All adverse events appeared in the first 72 hours post inoculation and lasted no longer than 3 days. One event was reported that was classified as severe in intensity and serious in consequences, but it was unrelated to vaccination—acute appendicitis in one individual inoculated with the control vaccine. Before vaccination, all participants but one had antibody concentrations ≥0.20 μg/ml against the vaccine strains; after vaccination 100% of individuals were positive and the concentrations of antibodies increased in previously positive volunteers. Some individuals had opsonophagocytic antibodies against serotypes 1, 14, 19F and 23F before vaccination, with highest concentrations against serotypes 14 and 19F. After vaccination, the percent of individuals with opsonophagocytic titers ≥1:8 for all serotypes in the vaccine was >50% in both groups. CONCLUSIONS A single dose of candidate vaccine PCV7-TT was safe when used in healthy adults. Preliminary results showed that it was able to activate an immune response against the serotypes of Streptococcus pneumoniae used.

Streptococcus pneumoniae causes annually 826 000 deaths in children under five years. The serotype 6B, one of higher incidence, is targeted by the Cuban research and development project to develop a conjugate vaccine. There is limited data on how modifications caused by conjugation affect the physicochemical and antigenic characteristics of polysaccharides, particularly for serotype 6B capsular polysaccharide (PS6B), despite being the least immunogenic among S. pneumoniae polysaccharides. In this work, a conjugation procedure was established for PS6B comprising: fragmentation by acid hydrolysis, activation by periodate oxidation, and conjugation to tetanus toxoid (TT) by reductive amination to increase its immunogenicity. Reaction conditions were set to obtain the polysaccharide in three molecular size ranges (1-10, 10-30, 30-100 kDa) and levels of oxidation. PS6B fragmentation below 10 kDa and oxidation above 24 % of the repetitive units implied the loss of antigenicity. Polysaccharide length but not oxidation level had an impact on the physicochemical characteristics of the conjugates in the tested conditions. Unlike the native polysaccharide, conjugated 10-30 kDa and 30-100 kDa PS6B were immunogenic in rabbits, with evidence of thymus-dependent response. The procedure described supports obtaining PS6B-TT conjugates reproducibly in the 30-100 kDa and 10-30 kDa molecular size ranges and with 8-18 % oxidized repeat units, which are immunogenic.

Anualmente Streptococcus pneumoniae provoca 826 mil muertes de niños menores de cinco años. El estudio del serotipo 6B, uno de los de mayor incidencia, es uno de los objetivos del proyecto de investigación-desarrollo para obtener una vacuna conjugada en Cuba. La estrategia de conjugación del polisacárido capsular del serotipo 6B (PS6B) fue fragmentarlo mediante hidrólisis ácida, activarlo mediante oxidación con peryodato y conjugarlo a toxoide tetánico (TT) mediante aminación-reductiva. Existe poca información sobre cómo estas modificaciones afectan las características físico-químicas y antigénicas del polisacárido, en particular para PS6B, a pesar de ser el menos inmunogénico de los polisacáridos de S. pneumoniae. En tal sentido, se estableció un procedimiento para obtener conjugados inmunogénicos de PS6B a TT. Se crearon condiciones de reacción para obtener el polisacárido en tres rangos de tallas y niveles de oxidación. Se determinó que la fragmentación del polisacárido por debajo de 10 kDa y la oxidación de más del 24 % de las unidades repetitivas implican pérdida de antigenicidad. La talla del polisacárido tuvo impacto en las características físico-químicas de los conjugados en las condiciones evaluadas; no así el nivel de oxidación. A diferencia del polisacárido nativo, conjugados de PS6B de 10 a 30 kDa y 30 a 100 kDa fueron inmunogénicos en conejos, con evidencias de respuesta timo-dependiente. Los procedimientos que incluyen la obtención del PS6B de 10 a 30 kDa y 30 a 100 kDa con niveles de oxidación entre 8 y 18 % de las unidades repetitivas oxidadas, permitieron obtener conjugados a TT reproducibles e inmunogénicos.

Conjugate vaccines consisting of bacterial polysaccharides linked through a covalent bond to a carrier protein have a major impact on childhood immunization schemes which have dramatically decrease the incidence of bacterial infections. In the case of Streptococcus pneumoniae more than 90 serotypes have been reported, based on the structure of the polysaccharide capsules and at least 23 of them have demonstrated clinical importance. A limited number of 7 or more recently 10 and 13 are included in licensed conjugate vaccines. On the other hand, the increasing need for these vaccines worldwide requires the incorporation of new manufacturers who are facing highly complex technology since the entire conjugation process can not affect the structural features for which the polysaccharide is immunologically recognized. Our paper provides a conjugation procedure for the capsular polysaccharide of Streptococcus pneumoniae serotype 14. The process includes fragmentation, peryodic oxidation and subsequent conjugation to tetanus toxoid or diphtheria toxoid to the polysaccharide, each intermediate was characterized by physico-chemical methods. Yields higher than 50% were obtained in all reactions. The conjugates generated high titers of IgG specific antibodies and immunological memory. In conclusion, the procedure allows immunogenic conjugates of serotype 14.

Las vacunas conjugadas que consisten en polisacáridos bacterianos unidos a través de un enlace covalente a una proteína portadora, han tenido un gran impacto en los esquemas de vacunación infantil, disminuyendo de forma dramática la incidencia de infecciones bacterianas. En el caso de Streptococcus pneumoniae, a pesar de que se han descrito más de 90 serotipos basados en la estructura de las cápsulas polisacarídicas y que al menos 23 tienen una importancia clínica demostrada, solo un número limitado de siete, o más recientemente 10 y 13, están incluidocaracterísticas estructurales por las que el polisacárido es reconocido inmunológicamente. Este trabajo implementó un procedimiento de conjugacs en las vacunas conjugadas licenciadas. Por otra parte, la necesidad creciente de estas vacunas en el mundo requiere la incorporación de nuevos productores que se enfrentan a una elevada complejidad tecnológica, pues en todo el procedimiento de conjugación no se pueden afectar las ión para el polisacárido de la cápsula de Streptococcus pneumoniae serotipo 14. El procedimiento comprendió la fragmentación, oxidación peryódica y posterior conjugación del polisacárido a anatoxina tetánica o diftérica. Cada intermedio fue caracterizado por métodos físico-químicos. En todas las reacciones se obtuvieron rendimientos superiores al 50%. Los conjugados generaron altos títulos de anticuerpos específicos de tipo IgG y memoria inmunológica. Se concluyó que el procedimiento permitió la obtención de conjugados inmunogénicos de serotipo 14.

In a previous study conducted at the province of Cienfuegos with ENZYMEBA it was proved that the microscopic examination of stools for the diagnosis of intestinal amebiasis was associated with false diagnoses in that province. Physicians from Cienfuegos were surveyed in connection with the diagnosis and treatment of intestinal amebiasis to know the possible factors related to this problem. According to the analysis of the results, the adverse consequences of the overdiagnosis of intestinal amebiasis may be aggravated by the lack of perception of the problem and by their marked ignorance on important aspects of this parasitosis.

Se demostró, en un estudio previo realizado en la provincia de Cienfuegos, en el que se empleó ENZYMEBA, que en aquella provincia, el examen microscópico de heces para el diagnóstico de amebiasis intestinal se asociaba a falsos diagnósticos. Para conocer de los posibles factores asociados a este problema, se aplicó una encuesta a médicos de la provincia de Cienfuegos, relacionada con el diagnóstico y tratamiento de la amebiasis intestinal. Según el análisis de los resultados, las consecuencias adversas del sobrediagnóstico de amebiasis intestinal pudieran estar amplificadas por la ausencia de percepción del problema, y por el marcado desconocimiento que sobre importantes aspectos de esta parasitosis poseen.