Immunogenicity and safety assessment of a SARS-CoV-2 recombinant spike RBD protein vaccine (Abdala) in paediatric ages 3-18 years old: a double-blinded, multicentre, randomised, phase 1/2 clinical trial (ISMAELILLO study).

Background: COVID-19 in paediatric ages could result in hospitalizations and death. In addition, excluding children from vaccination could turn them into reservoirs of the SARS-COV-2. Safe and effective COVID-19 vaccines are urgently needed for large-scale paediatric vaccination. ISMAELILLO study aimed to evaluate safety and immunogenicity of two strengths of a new recombinant receptor-binding domain (RBD) protein vaccine (Abdala) in paediatric population. Methods: A double-blinded, multicentre, randomised, phase 1/2 clinical trial was conducted in nine polyclinics in the province of Camagüey, Cuba. Healthy children and adolescents were stratified according to age (3-11 years old, or 12-18 years old) and they were randomly assigned (1:1; block size four) in two dosage level groups of vaccine to receive three intramuscular doses of 25 µg or 50 µg of RBD, 14 days apart. Main safety endpoint was analyzed as the percentage of serious adverse reactions during vaccination up to 28 days after the third dose (Day 56) in participants who received at least one dose vaccination. The primary immunogenicity endpoint assessed was seroconversion rate of anti-RBD IgG antibody at day 56. The immunogenicity outcomes were assessed in the per-protocol population. This trial is registered with Cuban Public Registry of Clinical Trials, RPCEC00000381. Findings: Between July 15, 2021, and August 16, 2021, 644 paediatric subjects were screened, of whom 592 were enrolled after verifying that they met the selection criteria: firstly 88 were included in Phase 1 of the study and 504 who completed Phase 2. The vaccine was well tolerated. Injection site pain was the most frequently reported local event (143 [8·4%] of 1707 total doses applied), taking place in 66/851 (7·8%) in the 25 µg group and in 77/856 (9·0%) in the 50 µg. The most common systemic adverse event (AE) was headache: 23/851 (2·7%) in the 25 µg group and 19/856 (2·2%) in the 50 µg. Reactogenicity was mild or moderate in severity, represented in 75% of cases by local symptoms, completely resolved in the first 24-48 h. Twenty-eight days after the third dose, seroconversion anti-RBD IgG were observed in 98·2% of the children and adolescents (231/234) for the 50 µg group and 98·7% (224/228) for the 25 µg group without differences between both strength. The specific IgG antibody geometric mean titres (GMT) showed higher titres between participants who received Abdala 50 µg (231·3; 95% CI 222·6-240·4) compared to those who received 25 µg (126·7; 95% CI 121·9-131·7). The mean ACE2 inhibition %, were 59·4% for 25 µg, and for 50 µg, 72·9% (p < 0·01). Both strength elicited neutralising activity against the SARS-CoV-2, specifically (18·3; 95% CI 14·7-22·78) for Abdala 25 µg and (36·4; 95% CI 30·26-43·8) for 50 µg to the selected sample analyzed. Interpretation: Abdala vaccine was safe and well tolerated at both antigenic strength levels tested in participants aged between 3 and 18 years. Regarding immunogenicity, Abdala Vaccine stimulated the production of specific IgG antibodies against the RBD of SARS-CoV-2 as well as the production of ACE2 inhibition titres and neutralising antibodies (Nab) in children and adolescents. Funding: Centre for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba.

Vigilancia de los eventos adversos a la vacunación en Camagüey (2018)

Objetivo: Evaluar la vigilancia de los eventos adversos a la vacunación en Camagüey en 2018. Métodos: Investigación en servicios y sistemas de salud de tipo operacional, con diseño evaluativo, que abarcó desde el 1ro. de enero hasta el 31 de diciembre de 2018. La población de estudio quedó constituida por 355 trabajadores (149 médicos de la familia, 161 enfermeras de familia, 16 enfermeras vacunadoras y 29 gerentes del programa de vacunación). La información se obtuvo mediante observación, revisión documental y entrevistas. Para evaluar los componentes: estructura, procesos y resultados, se definieron diferentes criterios, indicadores y estándares. Resultados: La estructura se evaluó como definida. El 90,9 % de los indicadores relacionados con cobertura y capacitación de los recursos humanos obtuvo la puntuación máxima, y en los recursos materiales, solo en el 81,2 % de los vacunatorios se disponía del conjunto de modelos necesario para el trabajo y control. Los atributos de sensibilidad, simplicidad, flexibilidad, aceptabilidad, integralidad, oportunidad y capacidad de autorespuesta, se evaluaron satisfactoriamente (70 % o más del estándar propuesto); la sensibilidad alcanzó solo el 34,2 %. Se obtuvo una tasa de 150 eventos adversos por 105dosis aplicadas, pero sin eventos graves, y los resultados se consideraron útiles. Conclusiones: El sistema de vigilancia de eventos adversos a la vacunación en Camagüey cumplió con los estándares establecidos para la confiabilidad del programa de vacunación y la toma de decisiones: una estructura bien definida, procesos con buen funcionamiento y resultados muy útiles.

Objective: To evaluate the surveillance for adverse events to vaccination in Camagüey in 2018. Methods: Operational research in health services and systems, with an evaluative design, which covered from January 1 to December 31, 2018. The study population comprised 355 workers (149 family physicians, 161 family nurses, 16 nurse vaccinators, and 29 vaccination program managers). Information was obtained through observation, documentary review, and interviews. Different criteria, indicators, and standards were established for evaluating the structure, process and outcome components. Results: The structure was evaluated as defined. The maximum score was obtained in 90.9% of the indicators related to coverage and training of human resources. Regarding material resources, only 81.2% of the vaccination centers had the necessary set of templates to carry out the work and control. The attributes of sensitivity, simplicity, flexibility, acceptability, comprehensiveness, timeliness, and self-response capacity were evaluated satisfactorily (70% or more of the proposed standard); sensitivity reached only 34.2%. A rate of 150 adverse events per 105doses applied was obtained; severe events were not evidenced, and the results were considered useful. Conclusions: The surveillance system for adverse events to vaccination in Camagüey met the standards established for the reliability of the vaccination program and decision-making: a well-defined structure, well-functioning processes, and very useful outcomes.

[Reactogenicity associated to the intradermally administered inactivated poliovirus vaccine with a needle-free injector]. / Reactogenicidad asociada a la administración intradérmica de la vacuna de polio inactivada con un inyector sin aguja.

INTRODUCTION: As the goal of poliomyelitis eradication is about to be accomplished, the need for an affordable and appropriate inactivated poliovirus vaccine (IPV) for use in developing countries has become a target for WHO. OBJECTIVE: To evaluate the reactogenicity of the inactivated poliovirus vaccine. METHOD: An experimental-type multicenter study was conducted, as part of a Phase I-II controlled clinical randomized and blinded assay, in 471 healthy infants of both sexes born in July and August 2006 in Camagüey province. The parents of the children who met the inclusion criteria gave their consent in writing. The children received three doses of the inactivated poliovirus vaccine at 6, 10 and 14 weeks after birth. This vaccine came form the Institute of Sera in Denmark and had been approved for use in this assay by the Cuban regularoty authorities, Low 0.1 mL inactivated poliovirus vaccine dose was intradermally administered to the study group A in the anterolateral side of the left thigh using the needle-free injector called Biojector 2000. The usual 0.5 mL dose was intramuscularly administered on the same site using a pre-filled syringe. The adverse events were observed during the first hour, 24, 48, and 72 hours after the immunization, as well as 7 and 30 days afterwards. The pediatrician in charge of the health area evaluated the reactogenicity at first and then the family physician was in charge of observing the adverse events in the remaining period. RESULTS: The 79.6% of children in group A and 75% in group B completed the research protocol. Mild local adverse reactions prevailed, mainly induration, pain and redness at the injection site. CONCLUSION: the Clinical trial proved the safety of the inactivated poliovirus vaccine for intramuscular administration, and also showed the safety of the intradermal route of administration and of the needle-free injector.

Reactogenicidad asociada a la administración intradérmica de la vacuna de polio inactivada con un inyector sin aguja / Reactogenicity associated to the intradermally administered inactivated poliovirus vaccine with a needle-free injector

INTRODUCCIÓN: en la medida en que la meta de la erradicación de la poliomielitis llega a su concreción, la necesidad de contar con una vacuna de polio inactivada asequible y apropiada para el uso en países en vías de desarrollo se ha convertido en una meta para la Organización Mundial de la Salud. OBJETIVO: la evaluación de la reactogenicidad de la vacuna de polio inactivada. MÉTODOS: se realizó un estudio multicéntrico con diseño experimental, correspondiente a Fase I-II de un ensayo clínico controlado, aleatorio y a simple ciegas, en 471 lactantes sanos de ambos sexos nacidos entre los meses de julio y agosto de 2006 en Camagüey, cuyos padres brindaron su consentimiento por escrito y que cumplieron con los criterios de inclusión establecidos. Los niños recibieron a las 6, 10 y 14 semanas del nacimiento, tres dosis de vacuna de polio inactivada del Instituto de Sueros de Dinamarca, autorizada para su uso en esta investigación por las autoridades regulatorias nacionales. Al grupo de estudio A, se le administró por la vía intradérmica la dosis reducida de 0,1 mL de vacuna de polio inactivada en la cara anterolateral del muslo izquierdo utilizando el inyector sin aguja Biojector® 2000. El grupo control B recibió la dosis usual de 0,5 mL por la vía intramuscular profunda, administrada en el mismo sitio descrito antes con una jeringuilla prellenada. Se observaron los eventos adversos durante la primera hora, 24, 48, y 72 h subsiguientes, así como a los 7 y 30 d de administrada la vacuna. La reactogenicidad se evaluó inicialmente por el pediatra del área y luego por el médico de familia mediante la observación de los eventos adversos. RESULTADOS: 79,6 por ciento del total de niños asignados al grupo A y 75 por ciento del grupo B finalizaron el protocolo de investigación. No se detectaron eventos adversos moderados o serios. Predominaron las reacciones adversas locales menores, sobre todo induración, dolor y enrojecimiento en el sitio de la inyección. CONCLUSIÓN: el ensayo demostró la seguridad de la vacuna de polio inactivada para su uso por vía intramuscular y reconoció la seguridad del uso de la vía intradérmica y del inyector sin agujas.

INTRODUCTION: as the goal of poliomyelitis eradication is about to be accomplished, the need for an affordable and appropriate inactivated poliovirus vaccine (IPV) for use in developing countries has become a target for WHO. OBJECTIVE: to evaluate the reactogenicity of the inactivated poliovirus vaccine. METHOD: an experimental-type multicenter study was conducted, as part of a Phase I-II controlled clinical randomized and blinded assay, in 471 healthy infants of both sexes born in July and August 2006 in Camagüey province. The parents of the children who met the inclusion criteria gave their consent in writing. The children received three doses of the inactivated poliovirus vaccine at 6, 10 and 14 weeks after birth. This vaccine came form the Institute of Sera in Denmark and had been approved for use in this assay by the Cuban regularoty authorities, Low 0.1 ml inactivated poliovirus vaccine dose was intradermally administered to the study group A in the anterolateral side of the left thigh using the needle-free injector called Biojector ® 2000. The usual 0.5 mL dose was intramuscularly administered on the same site using a pre-filled syringe. The adverse events were observed during the first hour, 24, 48, and 72 hours after the immunization, as well as 7 and 30 days afterwards. The pediatrician in charge of the health area evaluated the reactogenicity at first and then the family physician was in charge of observing the adverse events in the remaining period. RESULTS: the 79.6 percent of children in group A and 75 percent in group B completed the research protocol. Mild local adverse reactions prevailed, mainly induration, pain and redness at the injection site. CONCLUSION: the clinical trial proved the safety of the inactivated poliovirus vaccine for intramuscular administration, and also showed the safety of the intradermal route of administration and of the needle-free injector.

Intervención educativa sobre infección intrahospitalaria / Educational intervention on acute respiratory infections

Las infecciones intrahospitalarias son complicaciones en las cuales se conjugan diversos factores de riesgo, que en su mayoría pueden ser susceptibles de prevención y control. El riesgo de enfermar, e incluso de morir, por una infección que no era el motivo de ingreso al hospital está estrechamente vinculado a la calidad de la atención en los hospitales. Objetivo: aplicar una intervención educativa sobre infección intrahospitalaria en trabajadores de unidades de alto riesgo del Hospital de Santa Cruz del Sur. Método: se realizó un estudio experimental de intervención desde el 1ro de enero al 31 de junio de 2008, para elevar el nivel de conocimientos sobre las infecciones intrahospitalarias en trabajadores de unidades de alto riesgo del Hospital de Santa Cruz del Sur Enrique Santiesteban Báez. Constituyeron el universo y muestra de estudio cuarenta y cuatro trabajadores de las unidades de alto riesgo, a los que se les aplicó un cuestionario el cual constituyó la fuente primaria de obtención de datos. Resultados: se observó que antes de recibir las labores educativas se consideraron escasos los conocimientos que poseen los trabajadores acerca de la infección intrahospitalaria, sus localizaciones, gérmenes más frecuentes, las normas de prevención y control de la sepsis nosocomial así como los tipos de lavados de manos. Conclusiones: al inicio de la investigación los trabajadores tenían poco conocimiento sobre las infecciones intrahospitalarias, luego de la intervención se logró un aumento significativo del mismo, por lo que se consideró efectiva la intervención.

Background: the high morbidity for acute respiratory infections continues affecting little children. Objective: to demonstrate the effectiveness of a educational intervention program on respiratory infections in children's mothers smaller than one year of life. Method: an educational intervention study was carried out, in forty-five doctor’s offices of the East Polyclinic of Camagüey municipality, from January 2007 to May 2008. The study universe was constituted by seventy-two mothers, with childbirth date from June 1st to August 31 2007. A survey was applied that contained the variables to study, before and after the educational intervention was applied. Results: the greatest number of mothers in the age from thirty to thirty-four years, of pre-university schooling and hard-working was found, knowledge were increased to 90,27 percent. Conclusions: after the intervention the level of knowledge on respiratory infections in mothers was increased. The effectiveness of the educational intervention was demonstrated.