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Background: Increased pediatric COVID-19 occurrence due to the SARS-CoV-2 Omicron variant has raised concerns about the effectiveness of existing vaccines. The protection provided by the SOBERANA-02-Plus vaccination scheme against this variant has not yet been studied. We aimed to evaluate the scheme's effectiveness against symptomatic Omicron infection and severe disease in children. Methods: In September 2021, Cuba implemented a mass pediatric immunization with the heterologous SOBERANA-02-Plus scheme: 2 doses of conjugated SOBERANA-02 followed by a heterologous SOBERANA-Plus dose. By December, before the Omicron outbreak, 95.4% of 2-18 years-old had been fully immunized. During the entire Omicron wave, we conducted a nationwide longitudinal post-vaccination case-population study to evaluate the real-world effectiveness of the SOBERANA-02-Plus scheme against symptomatic infection and severe disease in children without previous SARS-CoV-2 infection. The identification of COVID-19 cases relied on surveillance through first line services, which refer clinical suspects to pediatric hospitals where they are diagnosed based on a positive RT-PCR test. We defined the Incidence Rate ratio (IRR) as IRvaccinated age group/IRunvaccinated 1-year-old and calculated vaccine effectiveness as VE = (1-IRR)∗100%. 24 months of age being the 'eligible for vaccination' cut-off, we used a regression discontinuity approach to estimate effectiveness by contrasting incidence in all unvaccinated 1-year-old versus vaccinated 2-years-old. Estimates in the vaccinated 3-11 years-old are reported from a descriptive perspective. Findings: We included 1,098,817 fully vaccinated 2-11 years-old and 98,342 not vaccinated 1-year-old children. During the 24-week Omicron wave, there were 7003/26,241,176 person-weeks symptomatic COVID-19 infections in the vaccinated group (38.2 per 105 person-weeks in 2-years-old and 25.5 per 105 person-weeks in 3-11 years-old) against 3577/2,312,273 (154.7 per 105 person-weeks) in the unvaccinated group. The observed overall vaccine effectiveness against symptomatic infection was 75.3% (95% CI, 73.5-77.0%) in 2-years-old children, and 83.5% (95% CI, 82.8-84.2%) in 3-11 years-old. It was somewhat lower during Omicron BA.1 then during Omicron BA.2 variant circulation, which took place 1-3 and 4-6 months after the end of the vaccination campaign. The effectiveness against severe symptomatic disease was 100.0% (95% CI not estimated) and 94.6% (95% CI, 82.0-98.6%) in the respective age groups. No child death from COVID-19 was observed. Interpretation: Immunization of 2-11 years-old with the SOBERANA-02-Plus scheme provided strong protection against symptomatic and severe disease caused by the Omicron variant, which was sustained during the six months post-vaccination follow-up. Our results contrast with the observations in previous real-world vaccine effectiveness studies in children, which might be explained by the type of immunity a conjugated protein-based vaccine induces and the vaccination strategy used. Funding: National Fund for Science and Technology (FONCI-CITMA-Cuba).

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Introducción: La pandemia de COVID-19 puso a prueba la capacidad de respuesta de las instituciones hospitalarias, constituyó una oportunidad para el aprendizaje de condiciones habilitantes que permitieran el nacimiento de instituciones resilientes. Objetivos: Documentar el proceso de reorganización hospitalaria para garantizar la resiliencia durante el enfrentamiento de la pandemia en un hospital general. Exponer el proceso de reorganización de los servicios y las lecciones aprendidas. Métodos: Investigación en Sistemas y Servicios de Salud de tipo evaluativa. Horizonte temporal entre marzo de 2020 - diciembre de 2021. Diseño mixto con datos cualitativos y cuantitativos. Se describió la resiliencia utilizando el marco metodológico que soporta la reorganización de servicios. Se tuvieron en cuenta indicadores de hospitalización. La serie se dividió en tres etapas: pre shock, shock y post shock. Se utilizaron técnicas de consenso con criterios de expertos sobre indicadores de alertas y alarma. Resultados: Para atender el incremento de casos en los servicios de urgencia, de hospitalizaciones, y el riesgo de enfermar del personal sanitario, el hospital definió cuatro acciones principales: expansión interna, priorización de la funcionabilidad de los servicios, continuidad de programas estratégicos y vacunación de trabajadores como grupo de riesgo. Se detallan las lecciones aprendidas en las tres etapas. Conclusiones: La evidencia documental de los sistemas de trabajo de hospitales resilientes es muy limitada y sin consenso. El proceso de reorganización hospitalaria en Cienfuegos reflejó la capacidad de resiliencia y aportó lecciones para futuros enfrentamientos a enfermedades con potencial pandémico.

Introduction: The COVID-19 pandemic tested the response capacity of hospital institutions and was an opportunity to learn about enabling conditions that would allow the birth of resilient institutions. Objectives: Document the hospital reorganization process to guarantee resilience during the pandemic in a general hospital. Present the process of reorganization of services and the lessons learned from it. Methods: Evaluative research in Health Systems and Services. Temporal horizon between March 2020 - December 2021. Mixed design with qualitative and quantitative data. Resilience was also described using the methodological framework that supports the reorganization of services. Hospitalization indicators were taken into account. The series were divided into three stages: pre shock, shock and post shock. Consensus techniques were implemented with expert criteria on alert and alarm indicators. Results: In order to address the increase in cases in emergency services, hospitalizations, and the risk of health personnel becoming ill, the hospital defined four main actions: internal expansion, prioritization of the functionality of services, continuity of strategic programs and vaccination of health workers as a risk group. The lessons learned in the three stages are detailed. Conclusions: Documental evidence of resilient hospital work systems is very limited and without any unanimity. The hospital reorganization process in Cienfuegos reflected the capacity for resilience and contributed in lessons for future confrontations with pandemic potential diseases.

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To better guide dengue prevention and control efforts, the use of routinely collected data to develop risk maps is proposed. For this purpose, dengue experts identified indicators representative of entomological, epidemiological and demographic risks, hereafter called components, by using surveillance data aggregated at the level of Consejos Populares (CPs) in two municipalities of Cuba (Santiago de Cuba and Cienfuegos) in the period of 2010-2015. Two vulnerability models (one with equally weighted components and one with data-derived weights using Principal Component Analysis), and three incidence-based risk models were built to construct risk maps. The correlation between the two vulnerability models was high (tau > 0.89). The single-component and multicomponent incidence-based models were also highly correlated (tau ≥ 0.9). However, the agreement between the vulnerability- and the incidence-based risk maps was below 0.6 in the setting with a prolonged history of dengue transmission. This may suggest that an incidence-based approach does not fully reflect the complexity of vulnerability for future transmission. The small difference between single- and multicomponent incidence maps indicates that in a setting with a narrow availability of data, simpler models can be used. Nevertheless, the generalized linear mixed multicomponent model provides information of covariate-adjusted and spatially smoothed relative risks of disease transmission, which can be important for the prospective evaluation of an intervention strategy. In conclusion, caution is needed when interpreting risk maps, as the results vary depending on the importance given to the components involved in disease transmission. The multicomponent vulnerability mapping needs to be prospectively validated based on an intervention trial targeting high-risk areas.

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Background: SOBERANA-02 is a COVID-19 conjugate vaccine (recombinant RBD conjugated to tetanus toxoid). Phases 1/2 clinical trials demonstrated high immunogenicity, promoting neutralising IgG and specific T-cell response. A third heterologous dose of SOBERANA-Plus (RBD-dimer) further increased neutralising antibodies. The aim of this study is to evaluate the safety and efficacy of two immunisation regimes: two doses of SOBERANA-02 and a heterologous three-dose combination with SOBERANA-Plus added to it. Methods: From March 8th to June 24th, 2021 we conducted in Havana, Cuba a multicentre randomised, double-blind, placebo-controlled, phase-3 trial evaluating a two doses SOBERANA-02 scheme and a heterologous scheme with one dose SOBERANA-Plus added to it (RPCEC00000354). Participants 19-80 years were randomly assigned to receiving 28 days apart either the two or three dose scheme or placebo. The main endpoint was vaccine efficacy in preventing the occurrence of RT-PCR confirmed symptomatic COVID-19 at least 14 days after the second or third dose in the per-protocol population. We also assessed efficacy against severe disease and, in all participants receiving at least one vaccine/placebo dose, safety for 28 days after each dose. Findings: We included 44,031 participants (52.0% female, 48.0% male; median age 50 years, range 19-80 years; 7.0% black, 24.0% mixed-race, 59.0% white) in a context of initial Beta VOC predominance, with this variant being partially replaced by Delta near the trial's end. Vaccine efficacy in the heterologous combination was 92.0% (95%CI 80.4-96.7) against symptomatic disease. There were no severe COVID-19 cases in the vaccine group against 6 in the placebo group. Two doses of SOBERANA-02 was 69.7% (95%CI 56.5-78.9) and 74.9% (95%CI 33.7-90.5) efficacious against symptomatic and severe COVID-19, respectively. The occurrence of serious and severe adverse events (AE) was very rare and equally distributed between placebo and vaccine groups. Solicited AEs were slightly more frequent in the vaccine group but predominantly local and mostly mild and transient. Interpretation: Our results indicate that the straightforward to manufacture SOBERANA vaccines are efficacious in a context of Beta and Delta VOC circulation, have a favourable safety profile, and may represent an attractive option for use in COVID-19 vaccination programmes. Funding: This study received funds from the National Fund for Science and Technology (FONCI-CITMA-Cuba, contract 2020-20) of the Ministry of Science, Technology and Environment of Cuba.

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OBJECTIVES: To evaluate a heterologous vaccination scheme in children 3-18 years old (y/o) combining two SARS-CoV-2r- receptor binding domain (RBD)protein vaccines. METHODS: A phase I/II open-label, adaptive, and multicenter trial evaluated the safety and immunogenicity of two doses of FINLAY-FR-2 (subsequently called SOBERANA 02) and the third heterologous dose of FINLAY-FR-1A (subsequently called SOBERANA Plus) in 350 children 3-18 y/o in Havana Cuba. Primary outcomes were safety (phase I) and safety/immunogenicity (phase II) measured by anti-RBD immunoglobulin (Ig)G enzyme-linked immunoassay (ELISA), molecular and live-virus neutralization titers, and specific T-cells response. A comparison with adult immunogenicity and predictions of efficacy were made based on immunological results. RESULTS: Local pain was the unique adverse event with frequency >10%, and none was serious neither severe. Two doses of FINLAY-FR-2 elicited a humoral immune response similar to natural infection; the third dose with FINLAY-FR-1A increased the response in all children, similar to that achieved in vaccinated young adults. The geometric mean (GMT) neutralizing titer was 173.8 (95% confidence interval [CI] 131.7; 229.5) vs Alpha, 142 (95% CI 101.3; 198.9) vs Delta, 24.8 (95% CI 16.8; 36.6) vs Beta and 99.2 (95% CI 67.8; 145.4) vs Omicron. CONCLUSION: The heterologous scheme was safe and immunogenic in children 3-18 y/o. TRIAL REGISTRY: https://rpcec.sld.cu/trials/RPCEC00000374.

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The implementation of new control strategies for Aedes aegypti (Ae. Aegpyti), a vector of dengue, chikungunya, and Zika viruses, requires communities to adopt specific behaviors to achieve the success of these innovations. AIM: We evaluated the effect of an educational intervention based on the Precede-Proceed Model (PPM) and the Diffusion of Innovations Theory (DIT) for the control and prevention of diseases transmitted by Ae. aegypti through release of male mosquitoes infected with Wolbachia bacteria in a suburban town in Yucatan, Mexico. MATERIAL AND METHODS: From July 2019 to February 2020, a quasi-experimental study was carried out through an educational intervention (pre- and post-measurements) using quantitative-qualitative techniques, in a Yucatan suburban town where male mosquitoes with Wolbachia were released for the suppression of Ae. aegypti populations. Eleven educational workshops were attended by heads of household (n = 19) and schoolchildren (n = 11). Other 136 heads of household not attending the workshops received information individually. RESULTS: The educational intervention had a significant effect on the mean scores of the contributing and behavioral factors for adoption of innovation (p < 0.05) in the pre- and post-intervention measurements. CONCLUSION: Innovative methods for the control and prevention of diseases related to Aedes aegypti can be strengthened through educational interventions supported by sound methodologies. DESCRIPTORS: Community health education, Aedes aegypti, Wolbachia, Mexico.

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Introducción: Las manifestaciones clínicas de la COVID-19 se presentan con particularidades diferentes en cada momento epidemiológico. Objetivo: Examinar las características clínicas de pacientes en edad pediátrica con COVID-19 durante la fase aguda de hospitalización, en diferentes momentos epidemiológicos. Métodos: Estudio descriptivo, transversal realizado en la provincia de Cienfuegos. Se estudiaron 784 pacientes diagnosticados con COVID-19, entre marzo de 2020 y marzo de 2022. Se analizaron las variables: edad, sexo, procedencia, antecedentes patológicos personales, sintomatología inicial, clasificación clínica, complicaciones, estadía, evolución y momento epidemiológico. Resultados: Los niños más hospitalizados fueron los menores de cinco años (57 por ciento) con un discreto predominio del sexo femenino (52 por ciento). El 71 por ciento de la muestra no presentó comorbilidades. La forma sintomática de la enfermedad se manifestó en 57 por ciento de los pacientes, y la asintomática en 42 por ciento. Solo 1 por ciento presentó formas graves de la infección. El mayor porcentaje de casos sintomáticos se produjo en el momento epidemiológico en el cual prevaleció la cepa Ómicron. La fiebre, la tos, y la secreción nasal fueron, por ese orden, las manifestaciones clínicas predominantes. El 4 por ciento presentó neumonías, y hubo un fallecido en la serie. El 67 por ciento egresó después de una estadía entre uno, y seis días. Conclusiones: Se comprobaron diferencias en el comportamiento clínico de la COVID-19, en sus diferentes momentos epidemiológicos en Cienfuegos. La forma de presentarse la infección por SARS-CoV-2 puede ser similar a otras infecciones respiratorias virales. Esto requiere mantener la vigilancia de esta enfermedad en niños(AU)

Introduction: The clinical manifestations of COVID-19 are presented with different particularities at each epidemiological moment. Objective: To examine the clinical characteristics of pediatric patients with COVID-19 during the acute phase of hospitalization, at different epidemiological times. Methods: A descriptive, cross-sectional study was conducted in the province of Cienfuegos. 784 patients diagnosed with COVID-19 between March 2020 and March 2022 were studied. The following variables were analyzed: age, sex, origin, personal pathological history, initial symptomatology, clinical classification, complications, stay, evolution and epidemiological moment. Results: The most hospitalized children were children under five years of age (57 percent) with a slight predominance of females (52 percent). 71 percent of the sample had no comorbidities. The symptomatic form of the disease manifested itself in 57 percent of patients, and the asymptomatic in 42 percent . Only 1 percent had severe forms of the infection. The highest percentage of symptomatic cases occurred at the epidemiological moment in which the Ómicron strain prevailed. Fever, cough, and runny nose were, in that order, the predominant clinical manifestations. 4 percent of the patients had pneumonia, and there was one death in the series. 67 percent discharged after a stay of one to six days. Conclusions: Differences were found in the clinical behavior of COVID-19, in its different epidemiological moments in Cienfuegos. The way SARS-CoV-2 infection occurs may be similar to other viral respiratory infections. This requires maintaining surveillance for this disease in children(AU)

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Esta revisión tuvo como propósito explorar la distribución de serotipos y la resistencia antimicrobiana de Streptococcus pneumoniae en la población pediátrica de China a partir de literatura publicada en los últimos seis años. Se realizó una revisión de alcance a partir de PubMed y dos bases de datos de China: CNKI y WanFang Data. Del total de 196 artículos extraídos, se seleccionaron 14 estudios para esta revisión. Hay 13 artículos que analizan la distribución de serotipos de Streptococcus pneumoniae; los serotipos más frecuentemente registrados son: 19F, 19A, 23F, 14 y 6B. Hay 11 artículos que analizan la resistencia antimicrobiana de Streptococcus pneumoniae, la prevalencia de no susceptibles a la penicilina se encuentra en el rango de 0 % a 95,7 %. Los aislados son muy resistentes a eritromicina, clindamicina, tetraciclina y trimetoprima-sulfametoxazol; son resistentes a penicilina en meningitis neumocócica pero son sensibles a penicilina en otras enfermedades neumocócicas, además, son muy sensibles a levofloxacina, vancomicina y Linezolid. Se concluye que la vacuna antineumocócica conjugada 13 tiene alta cobertura en los serotipos de Streptococcus pneumoniae en los niños de China continental, por eso se recomienda su inclusión en el programa de vacunación infantil; al mismo tiempo, se debe tener en cuenta la aparición de la sustitución de serotipos. Por eso, se deben incluir más pacientes pediátricos o niños en las investigaciones, especialmente los menores de cinco años. Es necesaria una vigilancia de alta calidad a largo plazo sobre la distribución de serotipos y resistencia antimicrobiana de Streptococcus pneumoniae para el desarrollo de la prevención de enfermedades neumocócicas.

This review aimed to explore the serotype distribution and antimicrobial resistance of Streptococcus pneumoniae in the Chinese pediatric population based on literature published in the last six years. A scoping review was performed using PubMed and two Chinese databases: CNKI and WanFang Data. Of the total of 196 articles extracted, 14 studies were selected for this review. There are 13 articles that analyze the distribution of Streptococcus pneumoniae serotypes, the most frequently registered serotypes are: 19F, 19A, 23F, 14 and 6B. There are 11 articles that analyze the antimicrobial resistance of Streptococcus pneumoniae, the prevalence of non-susceptible to penicillin is in the range of 0% to 95.7%. Isolates are highly resistant to erythromycin, clindamycin, tetracycline, and trimethoprim-sulfamethoxazole; they are resistant to penicillin in pneumococcal meningitis but are sensitive to penicillin in other pneumococcal diseases, in addition, they are very sensitive to levofloxacin, vancomycin and Linezolid. It is concluded that the pneumococcal conjugate vaccine 13 has high coverage in Streptococcus pneumoniae serotypes in children from mainland China, therefore its inclusion in the childhood vaccination program is recommended; at the same time, the occurrence of serotype substitution should be taken into account. Therefore, more pediatric patients or children should be included in research, especially those under five years of age. Long-term, high-quality surveillance of the serotype distribution and antimicrobial resistance of Streptococcus pneumoniae is necessary for the development of pneumococcal disease prevention.

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RESUMEN Fundamento: las arbovirosis continúan siendo un problema de salud en el mundo y en Cuba. La vigilancia de estas enfermedades es hoy prioridad en muchos países. Objetivo: describir el actual sistema de vigilancia de las arbovirosis en Cienfuegos durante el año 2019. Métodos: se realizó una investigación en sistemas y servicios de salud. Se exploraron 10 servicios de vigilancia. El sistema se describió en términos de: componentes, definición de caso, fuentes y flujo de datos, arquitectura tecnológica y tipos de vigilancia. Se realizó revisión documental, aplicación de una lista de chequeo, entrevistas a informantes claves y análisis de serie cronológica de arbovirosis 2014-2019. Resultados: la vigilancia se articula en red a través de sus componentes. La definición de caso se modifica en períodos epidémicos. Existen varias fuentes de datos de las cuales se nutre el sistema, algunas recogen información no útil para la vigilancia. La vigilancia basada en indicadores es la que se utiliza, no así la vigilancia basada en eventos y no existe un sistema informatizado que integre toda la información lo cual puede limitar su validez. Conclusiones: el sistema de vigilancia de las arbovirosis en Cienfuegos comparte características con los que se desarrollan a nivel internacional, sin embargo se identificaron limitaciones que pueden conspirar con el funcionamiento de algunos de sus atributos, cuestión que habría que explorar en próximos estudios.

ABSTRACT Background: arboviruses continue to be a health problem in the world and in Cuba. Surveillance of these diseases is now a priority in many countries. Objective to describe the current arbovirus surveillance system in Cienfuegos during 2019. Methods The research was carried out in health systems and services. 10 surveillance services were explored. The system is described in terms of: components, case definition, data sources and flow, technological architecture, and types of surveillance. A documentary review, application of a checklist, interviews with key informants and analysis of the chronological series of arboviruses 2014-2019 were carried out. Results: surveillance is articulated in a network through its components. The case definition is modified in epidemic periods. There are several data sources from which the system feeds, some collect information that is not useful for surveillance. Surveillance based on indicators is what is used, but surveillance based on events is not, and there is no computerized system that integrates all the information, which can limit its validity. Conclusions: the arbovirus surveillance system in Cienfuegos shares characteristics with those developed internationally, however, limitations were identified that may conspire with the functioning of some of its attributes, an issue that should be explored in future studies.

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BACKGROUND: SOBERANA 02 has been evaluated in phase I and IIa studies comparing homologous versus heterologous schedule (this one, including SOBERANA Plus). Here, we report results of immunogenicity, safety, and reactogenicity of SOBERANA 02 in a two- or three-dose heterologous scheme in adults. METHOD: Phase IIb was a parallel, multicenter, adaptive, double-blind, randomized, and placebo-controlled trial. Subjects (n = 810) aged 19-80 years were randomized to receive two doses of SARS-CoV-2 RBD conjugated to tetanus toxoid (SOBERANA 02) and a third dose of dimeric RBD (SOBERANA Plus) 28 days apart; two production batches of active ingredients of SOBERANA 02 were evaluated. Primary outcome was the percentage of seroconverted subjects with ≥4-fold the anti-RBD immunoglobulin G (IgG) concentration. Secondary outcomes were safety, reactogenicity, and neutralizing antibodies. FINDINGS: Seroconversion rate in vaccinees was 76.3% after two doses and 96.8% after the third dose of SOBERANA Plus (7.3% in the placebo group). Neutralizing IgG antibodies were detected against D614G and variants of concern (VOCs) Alpha, Beta, Delta, and Omicron. Specific, functional antibodies were detected 7-8 months after the third dose. The frequency of serious adverse events (AEs) associated with vaccination was very low (0.1%). Local pain was the most frequent AE. CONCLUSIONS: Two doses of SOBERANA 02 were safe and immunogenic in adults. The heterologous combination with SOBERANA Plus increased neutralizing antibodies, detectable 7-8 months after the third dose. TRIAL REGISTRY: https://rpcec.sld.cu/trials/RPCEC00000347 FUNDING: This work was supported by Finlay Vaccine Institute, BioCubaFarma, and the Fondo Nacional de Ciencia y Técnica (FONCI-CITMA-Cuba, contract 2020-20).

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