Real-world effectiveness of the heterologous SOBERANA-02 and SOBERANA-Plus vaccine scheme in 2-11 years-old children during the SARS-CoV-2 Omicron wave in Cuba: a longitudinal case-population study.

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).

Temporal-Spatial Distribution of Vibrio cholerae in Cuba: July 1997-December 2019.

INTRODUCTION: Vibrio cholerae is a microorganism that causes acute diarrheal diseases and cholera, one of the leading causes of global morbidity and mortality, especially in children under five years old. It is present in many regions and has been isolated from diverse sources such as water, soil and food. Surveillance of this microorganism in Cuba from 1985 through June 1997 showed circulation of non-epidemic non-O1/non-O139 serogroups, but surveillance continued to identify distribution of V. cholerae serotypes and serogroups in the different geographic regions of the country during the following years, due to the risk of introducing cholera-causing serogroups that provoked cholera epidemics in other countries of the region. OBJECTIVE: Describe the temporal‒spatial distribution of serogroups and serotypes of V. cholerae in Cuba. METHODS: A cross-sectional study was conducted that included isolates from passive surveillance of V. cholerae in 16 hygiene and epidemiology centers throughout Cuba from July 1997 through December 2019, submitted to the National Reference Laboratory for Acute Diarrheal Diseases of the Pedro Kourí Tropical Medicine Institute in Havana, Cuba. The timeline was subdivided into three five-year periods and one eight-year period. The centers submitting isolates were grouped into three geographical regions: western, central and eastern Cuba. A total of 1060 V. cholerae isolates were studied, from the 1438 samples sent from 15 Provincial Hygiene, Epidemiology and Microbiology Centers and the Municipal Hygiene, Epidemiology and Microbiology Center of the Isle of Youth Special Municipality. Genus, species and serotype of all specimens were studied and reviewed in the context of the outbreaks of acute diarrheal diseases reported in the country. RESULTS: All 1060 isolates were confirmed as V. cholerae. In the distribution by time period and region, the highest percentage occurred in the 2012‒2019 period, and the eastern region contributed the most isolates in all periods. Approximately 63.9% (677/1060) were from outbreaks, and in the 2012‒2019 period, the most epidemic-causing isolates came from the western region. Approximately 52.8% (560/1060) were identified as non-O1/non-O139 V. cholerae, and 47.2% (500/1060) as O1 V. cholerae; of these, 96.4% (482/500) corresponded to Ogawa serotype and 3.6% (18/500) to Inaba. Circulation of non-O1/non-O139 V. cholerae occurred throughout the entire period. The O1 serogroup began to circulate in 2012 and continued through 2016; however, since 2017, it has not been identified again. In the western region, there were smaller percentages of isolates of non-O1/non-O139 V. cholerae in all periods, except 2012‒2019. In that period, V. cholerae O1 was identified to a lesser degree in the central region. CONCLUSIONS: Vibrio cholerae circulated in all three Cuban regions during the years studied, with a higher percentage of isolates of the non-O1/non-O139 serogroup, which caused outbreaks or sporadic cases of diarrhea in the eastern region, with the exception of the 2012‒2019 period, when epidemic outbreaks of the O1 serogroup (which causes cholera) occurred in all three regions, with higher percentages in the western region.

Factores asociados a la distribución espacial de la tuberculosis en La Habana, 2015 / Factors associated with the spatial distribution of tuberculosis in Havana, 2015

Introducción: El año 2015 es el marco de referencia temporal internacional para evaluar las acciones de la estrategia Fin a la tuberculosis. La eliminación de la enfermedad como problema de salud requiere de la identificación de poblaciones y territorios en mayor riesgo, y de los determinantes de su distribución geográfica. Objetivo: Determinar la influencia de factores socioeconómicos, demográficos y geoespaciales en la distribución espacial de la tuberculosis en La Habana en el año 2015. Métodos: Se realizó un estudio ecológico. Se describió la distribución espacial del total de casos de tuberculosis, la confección TB/VIH y los casos TB/reclusos a nivel de municipio; así como de variables socioeconómicas, demográficas y geoespaciales con datos disponibles de todos los municipios de la provincia. Se realizaron mapas temáticos para cada una de las variables. Posteriormente, se realizó un análisis de superposición de capas. Resultados: Se observó una mayor concentración de casos en el centro-sur de la provincia; principalmente en los municipios Centro Habana, Habana Vieja, Diez de Octubre y Boyeros, a excepción de este último, estos municipios son los más densamente poblados, los que tienen mayor ocupación del suelo y condiciones de vida más desfavorables. Conclusiones: La distribución espacial de la tuberculosis en La Habana está estrechamente relacionada al comportamiento de variables socioeconómicas, demográficas y geoespaciales en sus diferentes municipios. Estas variables deben ser tomadas en cuenta en intervenciones de salud dirigidas a la eliminación de la enfermedad en la provincia(AU)

Introduction: The year 2015 constitutes the international time frame of reference to evaluate the actions of the End tuberculosis strategy. The elimination of the disease as a health problem requires the identification of populations and territories at greatest risk, and the determinants of their geographical distribution. Objective: Determine the influence of socio-economic, demographic and geospatial factors on the spatial distribution of tuberculosis in Havana in 2015. Methods: An ecological study was conducted. The spatial distribution of total TB cases, TB/HIV and TB/inmate cases at the municipality level was described; as well as socio-economic, demographic and geospatial variables with data available from all municipalities in the province. Thematic maps were made for each of the variables. Subsequently, a layer overlap analysis was performed. Results: A higher concentration of cases was observed in the center-south of the province; mainly in the municipalities of Centro Habana, Habana Vieja, Diez de Octubre and Boyeros ; with the exception of the latter, these municipalities are the most densely populated, those with the highest land occupation and the most unfavorable living conditions. Conclusions: The spatial distribution of tuberculosis in Havana is closely related to the behavior of socio-economic, demographic and geospatial variables in its different municipalities. These variables should be taken into account in health interventions aimed at eliminating the disease in the province(AU)

Estratificación espacial de la tuberculosis en menores de 15 años de edad en las provincias occidentales de Cuba, 2011-2015 / Spatial stratification of tuberculosis in the western provinces of Cuba, 2011-2015 in children under 15 years

Introducción: La tuberculosis infantil posee baja incidencia en Cuba, no obstante, se considera un indicador de transmisión reciente de la enfermedad. Objetivo: Estratificar espacialmente la tuberculosis en menores de 15 años de edad en la región occidental de Cuba en el periodo 2011-2015, según las metas progresivas hacia la eliminación de la enfermedad. Métodos: Se realizó un estudio ecológico de series temporales. La estatificación espacial de la tuberculosis se realizó a partir de técnicas geoespaciales que asignan a cada territorio valores ponderados graduados con respecto a los rangos establecidos de las medias geométricas de las tasas de notificación en el periodo. Los estratos se corresponden con las metas progresivas hacia la eliminación de la tuberculosis. Resultados: Se encontraron en la categoría de ultracontrol muy avanzado las provincias La Habana [municipios Plaza de la Revolución (2,4), Centro Habana (3,7), San Miguel del Padrón (2,1), Diez de Octubre (1,6) y Marianao (1,0)], Mayabeque [Melena del Sur (3,5) y San José de las Lajas (1,4)] y Matanzas [Unión de Reyes (1,1)]. Conclusiones: La presencia de diferentes estratos geoespaciales de la tuberculosis en menores de 15 años de edad en la región occidental de Cuba constata la necesidad de diseñar estrategias que se adecuen a la realidad de los diferentes territorios. El abordaje geoespacial fortalece la estratificación epidemiológica de acuerdo a las metas progresivas hacia la eliminación de la tuberculosis(AU)

Introduction: Children tuberculosis has a low incidence in Cuba, however, it is considered an indicator of recent transmission of the disease. Objective: Spatially stratify tuberculosis in children under 15 years of age in the western region of Cuba in the period 2011-2015, according to the progressive goals towards the elimination of the disease. Methods: An ecological time series study was conducted. The spatial stratification of tuberculosis was carried out from geospatial techniques that assign to each territory weighted values graded with respect to the established ranges of the geometric means of the notification rates in the period. The strata correspond to the progressive goals towards the elimination of tuberculosis. Results: The provinces of Havana [municipalities : Plaza de la Revolución (2.4), Centro Habana (3.7), San Miguel del Padrón (2.1), Diez de Octubre (1.6) and Marianao (1.0)], Mayabeque (municipalities : Melena del Sur (3.5) and San José de las Lajas (1.4)] and Matanzas [municipalities : Unión de Reyes (1.1)] were found in the category of very advanced ultracontrol. Conclusions: The presence of different geospatial strata of tuberculosis in children under 15 years of age in the western region of Cuba confirms the need to design strategies that adapt to the reality of the different territories. The geospatial approach strengthens the epidemiological stratification according to the progressive goals towards the elimination of tuberculosis(AU)

Detección prospectiva espacio-temporal de conglomerados de COVID-19 en Cuba

RESUMEN Introducción: Durante enfermedades infecciosas emergentes en curso como la COVID-19, la vigilancia espacio-temporal es fundamental para identificar áreas prioritarias para intervenciones específicas, diferenciar intensidad diagnóstica y asignación de recursos. Objetivo: Modelar la evolución del riesgo relativo de presentación de casos de COVID-19 e identificar conglomerados en municipios donde la enfermedad se mantuvo en el periodo posterior al descenso de la curva epidémica en Cuba. Métodos: El periodo mencionado comprendió entre el 26/05/2020 hasta el 4/09/2020. Se realizaron corridas cíclicas del modelo prospectivo espacio-temporal de Poisson, con incrementos progresivos de 14 días, mediante la aplicación SaTScan™ 9.6. Resultados: Se identificaron 15 conglomerados significativos (p ≤ 0,0001) cuya extensión involucró desde uno hasta trece municipios, con distribución en seis provincias (Pinar del Río, Artemisa, La Habana, Mayabeque, Matanzas, Villa Clara y Ciego de Ávila). En los conglomerados todos los municipios mostraron riesgo relativo alto, entre ellos, La Palma en la provincia de Pinar del Río y Ciego de Ávila en la provincia del mismo nombre, con los valores más altos, 119,95 y 121,04, respectivamente. Conclusión: El modelo empleado pudo identificar los conglomerados en territorios con significativa probabilidad de ocurrencia de COVID-19, así como periodos de evolución del riesgo relativo. Además, reconoce los municipios que merecen prioridad para intensificar en ellos intervenciones de contención y control sanitario y evitar la reemergencia de la enfermedad con mayor dispersión espacial.

ABSTRACT Introduction: During the occurrence of ongoing emerging infectious diseases such as COVID-19, spatiotemporal surveillance is crucial to identify priority areas for specific interventions, differentiate diagnostic intensity and assign resources. Objective: To model the evolution of the relative risk of presentation of COVID-19 cases and to identify clusters in municipalities where the disease remains at the stage following the descent of the epidemic curve in Cuba. Methods: The period mentioned was from 26/05/2020 to 4/09/2020. Cyclic runs of Poisson's prospective spatiotemporal model were performed, with progressive 14-day increases, using the software SaTScan™ 9.6. Results: A total 15 significant clusters were identified (p ≤ 0.0001) extending over one to thirteen municipalities and distributed in six provinces (Pinar del Río, Artemisa, Havana, Mayabeque, Matanzas, Villa Clara and Ciego de Ávila). In the clusters, all municipalities showed a high relative risk among them, La Palma in Pinar del Rio province and Ciego de Avila in the province of the same name, with the highest values, 119.95 and 121.04, respectively. Conclusion: The model was able to identify territories with a significant likelihood of COVID-19 occurrence, as well as periods in the evolution of relative risk. It also showed that surveillance and early warning strategies may facilitate prioritization of health control and containment interventions aimed at preventing the reemergence of the disease with greater spatial coverage.