Seguridad de las vacunas SOBERANAS® en niños, hijos de trabajadores de una institución de BioCubaFarma / Safety of SOBERANAS® vaccines in children of workers of a BioCubaFarma institution

En un complejo contexto epidemiológico nacional e internacional, de trasmisión y hospitalización por COVID-19 en población pediátrica, Cuba decidió realizar una campaña de vacunación masiva contra esta enfermedad en niños y adolescentes. El objetivo de este trabajo fue evaluar la seguridad del esquema heterólogo de dos dosis de SOBERANA®02 más una dosis de SOBERANA®Plus con 28 días entre ellas en niños y adolescentes, hijos de los trabajadores del Centro Nacional de Biopreparados, que pertenece a BioCubaFarma, Grupo Empresarial de las Industrias Biotecnológica y Farmacéutica de Cuba. La seguridad de las vacunas se evaluó mediante la identificación y clasificación de los eventos adversos por farmacovigilancia activa y pasiva. Se evaluaron 237 niños de ambos sexos, siendo incluidos 200 (130 con edades de 2 a 10 años y 70, de 11 a 18). Ciento noventa niños de los incluidos (95 por ciento) recibieron el esquema completo de vacunación. Se registraron un total de 121 eventos adversos, en su mayoría por farmacovigilancia pasiva, de intensidad leve y de causalidad A1 (relacionados). No ocurrieron eventos adversos graves relacionados. Las vacunas SOBERANA®02 y SOBERANA®PLUS evidenciaron un perfil de seguridad muy favorable durante su administración a niños y adolescentes, hijos de los trabajadores del Centro Nacional de Biopreparados(AU)

In a complex national and international epidemiological context of transmission and hospitalization by COVID-19 in the pediatric population, Cuba decided to carry out a massive vaccination campaign against this disease in children and adolescents. The aim of this work was to evaluate the safety of the heterologous scheme of two doses of SOBERANA®02 and one dose of SOBERANA®PLUS with 28 days between them, in children and adolescents who are sons of workers of the Centro Nacional de Biopreparados which belongs to BioCubaFarma, the Business Group of the Biotechnological and Pharmaceutical Industries of Cuba. The safety of the vaccines was evaluated through the identification and classification of adverse events by active and passive pharmacovigilance. A quantity of 237 children of both sexes was evaluated, and 200 were included (130 from 2 to 10 years, and 70 from 11 to 18 years). Of those included, 190 children (95percent) received the complete vaccination schedule. A total of 121 adverse events were recorded, mostly due to passive pharmacovigilance, of mild intensity and A1 (related) causality. No related serious adverse events occurred. The SOBERANA®02 and SOBERANA®PLUS vaccines showed a very favorable safety profile during their administration to children and adolescents who are sons of workers at the Centro Nacional de Biopreparados(AU)

Prevalence of Alzheimer's disease in rural and urban areas in Cuba and factors influencing on its occurrence: epidemiological cross-sectional protocol.

INTRODUCTION: According to the World Alzheimer's Report 2019, around 50 million people suffer from dementia, worldwide. Observational analysis revealed the existence of particular factors associated with the onset and progression of Alzheimer's disease (AD). There are no international homogeneous principles for the early detection and evaluation of memory impairment and possible AD. This work aimed at (1) determining the prevalence of possible AD in the elderly residing in urban and rural regions in Cuba and (2) identifying the main factors that could significantly influence on its occurrence. METHODS AND ANALYSIS: The study includes four neuropsychological tests (Clock Drawing Test, Mini-Mental Status Examination, Short Portable Mental Status Questionnaire, Cognitive and Non-Cognitive Alzheimer's Disease Assessment Scale) and two scales (Clinical Dementia Rating and Global Deterioration Scale). Moreover, the protocol includes a survey with demographic and socioeconomic information, educational level, occupation, health, neuropsychological status of subjects, familial pathological history, comorbidities and lifestyles. The study will comprise a total of 1092 subjects aged ≥60, of both genders, and from every ethnic group settled in rural and urban areas. PRIMARY OUTCOMES: prevalence of possible AD. SECONDARY OUTCOMES: correlation among risk and protective factors and AD, and comparison of the performance of neuropsychological tests and scales. ETHICS AND DISSEMINATION: This research met the ethical codes of the Declaration of Helsinki. The Scientific Research Council of the Promoting Research Institute and the Ethics Committee of the Health Authorities approved the protocol. The proper written informed consent is also incorporated. The results of the survey will be published in scientific papers and shared with the Health Authorities of each municipality.

Estudio de intervención con SOBERANA® en los trabajadores del Centro Nacional de Biopreparados / Intervention study with SOBERANA® in the workers of the Centro Nacional de Biopreparados

Se presentan los resultados del estudio de intervención realizado en el Centro Nacional de Biopreparados, empresa de BioCubaFarma. La investigación fue promovida por el Instituto Finlay de Vacunas, con el objetivo de evaluar los efectos directos e indirectos de la vacunación anti SARS-CoV-2 con un esquema heterólogo 2P+1: dos dosis de SOBERANA®02 más una dosis de SOBERANA®Plus con 28 días entre ellas, en cohortes poblacionales de riesgo de infección, enfermedad y dispersión de la epidemia. Fueron evaluados 1.007 sujetos, incluyéndose inicialmente 924. De ellos, el 97,62 por ciento recibió el esquema completo de vacunación. Posteriormente se incluyeron 21 convalecientes de COVID-19 con al menos dos meses del alta clínica, que recibieron una única dosis de SOBERANA®Plus. La seguridad de las vacunas se evalúo mediante la identificación y clasificación de los eventos adversos por farmacovigilancia activa y pasiva. Se registraron un total de 482 eventos adversos, en su mayoría por farmacovigilancia pasiva, de intensidad leve y de causalidad A1 (relacionados). No ocurrieron eventos adversos graves relacionados. Se realizó cuantificación de IgG anti SARS-CoV-2 a 100 individuos y el 68 por ciento tuvo una respuesta mayor o igual de 50 UA/mL, siendo estos sujetos nueve años menores que los de respuesta menor. Hasta los tres meses de concluida la intervención, 64 vacunados fueron diagnosticados con COVID-19 y ninguno de ellos estuvo grave o falleció. Se evidenció un perfil de seguridad muy favorable de SOBERANA® e indicios de efectividad en la prevención de formas graves y mortalidad por COVID-19(AU)

The results of an intervention study performanced at the Centro Nacional de Biopreparados, a company of BioCubaFarma, are presented. The research was promoted by the Finlay Vaccine Institute, with the aim of evaluating the direct and indirect effects of vaccination against SARS-CoV-2, with a heterologous 2P + 1 scheme: two doses of SOBERANA®02 plus one dose of SOBERANA®Plus with 28 days between them; in population cohorts at risk of infection, disease and spread of the epidemic. A quantity of 1,007 subjects were evaluated and 924 were initially included. Of these, 97.62 percent received the complete vaccination schedule. Subsequently, 21 convalescents of COVID-19 with at least two months of clinical discharge were included, who received a single dose of SOBERANA®Plus. The safety of the vaccine was evaluated by identifying and classifying adverse events by active and passive pharmacovigilance. A total of 482 adverse events were recorded, mostly due to passive pharmacovigilance, mild intensity and A1 causality (related). No related serious adverse events occurred. IgG anti SARS-CoV-2 was quantified in 100 individuals, and 68 percent had a response greater than or equal to 50 IU/mL, these subjects being nine years younger than those with a lower response. Up to three months after the intervention, 64 vaccinated people were diagnosed with COVID-19 and none of them were seriously ill or died. A very favorable safety profile of SOBERANA® and indications of effectiveness in preventing severe forms and mortality from COVID-19 were evidenced(AU)

Biomodulina T® como alternativa de tratamiento en el shock séptico en pediatría / Biomodulina T® as an alternative to the treatment of septic shock in pediatrics

Introducción: La sepsis y el shock séptico se encuentran entre las principales causas de morbilidad y mortalidad en la población pediátrica a nivel mundial. Encontrar soluciones alternativas para combatirlas, mediante el desarrollo de agentes inmunomoduladores, ha atraído el interés de investigadores en los últimos 20 años; Cuba cuenta con Biomodulina T®, un potente inmunomodulador. Objetivo: Demostrar que existe evidencia científica que avale la realización de ensayos clínicos controlados para la incorporación de la Biomodulina T® en las pautas de tratamientos de la sepsis en las terapias intensivas pediátricas. Material y Métodos: Se realizó una búsqueda en las bases de datos Medline, PubMed, SciELO, Lilacs, Cochrane Library y Web of Science, entre marzo de 2019 y marzo de 2020; se seleccionaron los 47 artículos de mayor relevancia para esta investigación. Desarrollo: La inmunopatogenia del shock se centra en un fenotipo complejo y alteraciones funcionales, tanto del sistema inmune innato como del sistema adaptativo, con disminución del número de células efectoras, aumento de subpoblaciones de linfocitos inmunosupresores y agotamiento de células T. Biomodulina T® estimula la producción de linfocitos T y robustece la diferenciación de las células linfoblastoides del timo. La práctica médica sugiere que su administración podría ser una estrategia prometedora para la restauración inmune en pacientes pediátricos con shock séptico. Conclusiones: Existe evidencia científica que respalda el uso de Biomodulina T® en pacientes con shock séptico, lo cual sustenta la fiabilidad de realizar ensayos clínicos controlados en población pediátrica para su posterior incorporación en las pautas de tratamientos en las terapias intensivas(AU)

Introduction: Sepsis and septic shock are among the main causes of morbidity and mortality in the pediatric population worldwide. Finding alternative solutions to combat them through the development of immunomodulatory agents has attracted the interest of researchers in the last 20 years; Cuba has Biomodulina T®, a powerful immunomodulator. Objective: To demonstrate that there is scientific evidence that supports the conduction of controlled clinical trials for the incorporation of Biomodulina T® into the treatment guidelines for sepsis in pediatric intensive care therapies. Material and Methods: A search was carried out in the Medline, PubMed, SciELO, Lilacs, the Cochrane Library and the Web of Science databases between March 2019 and March 2020; the 47 most relevant articlesfor this research were selected. Development: The immunopathogenesis of shock focuses on a complex phenotype and functional alterations of both the innate and adaptive immune systems with a decrease in the number of effector cells, an increase in subpopulations of immunosuppressive lymphocytes, and depletion of T cells. Biomodulina T® stimulates the production of T lymphocytes and strengthens the differentiation of lymphoblastoid cells of the thymus; medical practice suggests that its administration could be a promising strategy for immune restoration in pediatric patients with septic shock. Conclusions: There is scientific evidence that supports the use of Biomodulina T® in patients with septic shock, which supports the reliability of conducting controlled clinical trials in the pediatric population for its subsequent incorporation into treatment guidelines in intensive care therapies(AU)

Is peanut causing food allergy in Cuba? Preliminary assessment of allergic sensitization and IgE specificity profile to peanut allergens in Cuban allergic patients.

BACKGROUND: Peanut allergy is increasing at an alarming pace in developed countries. Peanut (Arachis hypogaea) is a common food in Cuba. Nevertheless, reported values of sensitization and symptom severity are usually low. As our objective, we carried out an evaluation of allergic sensitivity to perform an assessment of allergic sensitization and IgE specificity profile to peanut allergens in Cuban allergic patients. METHODS: The Skin Prick Test (SPT) was performed for each patient, using two glycerinated allergenic extracts, prepared from raw or roasted peanuts. Overall, 316 food allergic patients (159 adults and 157 children) attending allergy services at four hospitals in Havana were included, as well as 303 adult non- allergic volunteers. The IgE binding profile of 26 selected SPT positive patients was further analyzed by immunoblotting. RESULTS: The prevalence of sensitization to peanut was 4.6% in general adult population, whereas in adult food-allergic patients it was 18.6%. Prevalence rates were even greater in food allergic children achieving 25.8%. Sensitization frequencies were apparently greater for roasted, as compared to raw peanuts, although the difference was not significant (p> 0.05, Mc Nemar's). IgE binding was shown mostly by the 15 and 17 kDa bands, tentatively identified as the major allergens Ara h 2 and Ara h 6. The IgG4 binding profile was similar to IgE, although with more prominence of the bands at 37 and 28 KDa, corresponding to an Ara h 3 fragment and Peanut Agglutinin. DISCUSSION: The study estimated a relatively high prevalence of peanut sensitization in population. Data reported here suggest that IgE sensitization in Cuban patients is focused mostly on MW bands corresponding to the major allergens Ara h 6 and Ara h 2. CONCLUSIONS: Sensitization to peanut allergen is indeed relatively frequent in Cuba. The IgE profile is congruent to a sensitization pattern by ingestion of roasted peanuts and is directed to well-known major allergens.

[Sensitivity and specificity of prick skin test with two concentrations of standardized extract of Culex quinquefasciatus in allergic children]. / Sensibilidad y especificidad de la prueba cutánea por punción con dos concentraciones del extracto estandarizado de Culex quinquefasciatus en niños alérgicos.

BACKGROUND: Diagnostic options for immune reactions to mosquito bites are limited. In Cuba, IgE-mediated reactions are frequently related to Culex quinquefasciatus bite. OBJECTIVE: To determine the sensitivity and specificity of skin prick test with two doses of standardized extract in nitrogen protein units (PNU of Culex quinquefasciatus (BIOCEN, Cuba). MATERIAL AND METHOD: An analytical study was conducted on 100 children between 2 and 15 years old. Fifty atopic patients with a history of allergy to mosquito bite and positive specific serum IgE Culex quinquefasciatus and fifty atopic patients without a history of allergy to mosquito bite and negative specific serum IgE to Culex quinquefasciatus. Skin prick tests (SPT) were performed by duplicates on the forearms of the patients. Investigated doses were 100 PNU/mL and 10 PNU/mL. RESULTS: SPT with the highest concentration obtained a mean wheal size of 22.09 mm2 and for lower doses of 8.09 mm2, a statistically significant difference (p=0.001, Student's t test). Positive skin test correlated in 100% of patients with the presence of specific IgE. Testing with both doses showed a 94% of specificity and 88% of sensitivity. CONCLUSION: The diagnostic accuracy of SPT using both doses of standardized extract was similar, which justifies its use for diagnosis of sensitization to Culex quinquefasciatus in patients with symptoms of allergy to mosquito bite.

Antecedentes: las opciones diagnósticas de las reacciones inmunológicas a la picadura del mosquito son limitadas. En Cuba, las reacciones mediadas por IgE más frecuentes son por picadura de Culex quinquefasciatus. Objetivo: determinar la sensibilidad y especificidad de la prueba cutánea por punción con dos dosis del extracto estandarizado en unidades de nitrógeno proteico (UNP) de Culex quinquefasciatus (BIOCEN, Cuba). Material y método: estudio analítico efectuado en 100 niños entre 2 y 15 años de edad: 50 pacientes atópicos con antecedentes de alergia a la picadura de mosquito e IgE sérica específica positiva a Culex quinquefasciatus y 50 pacientes atópicos sin antecedentes de alergia a la picadura de mosquito e IgE sérica específica negativa a Culex quinquefasciatus. La prueba cutánea por punción se realizó por duplicado en los antebrazos de los pacientes. Las dosis investigadas fueron 100 y 10 UNP/mL. Resultados: en la prueba cutánea por punción con el extracto de mayor concentración se obtuvo un tamaño del área del habón de 22.09 mm2 y con la menor concentración de 8.19 mm2; una diferencia estadísticamente significativa (p=0.001, prueba t de Student). La prueba cutánea positiva se correlacionó en el 100% de los pacientes con la existencia de IgE específica. La prueba con ambas dosis mostró 94% de especificidad y 88% de sensibilidad. Conclusión: la alta coincidencia en el resultado de la prueba cutánea nos muestra que puede sustituirse la concentración del extracto a 100 UNP/mL por la de menor concentración, sin perder confiabilidad en el diagnóstico de sensibilización al mosquito Culex quinquefasciatus, utilizando ese método in vivo.

[Sensitization to three house dust mites in a children allergic population of cuba]. / Sensibilización a tres ácaros domésticos en una población infantil alérgica de Cuba.

BACKGROUND: Allergic diseases constitute a worldwide health problem and mites are among the main etiological agents. OBJECTIVE: To characterize the sensitization to the mites Dermatophagoides pteronyssinus, Dermatophagoides siboney, and Blomia tropicalis, by skin tests in a children allergic sample from Cuba. METHODS: This is a descriptive transversal investigation that included 103 allergic children, with ages ranging from 3 to 15 years, who underwent skin prick tests with D. pteronyssinus, D. siboney, and B. tropicalis allergenic extracts. For the analysis of the results, sex, place of residence and degree of exposure to house dust were considered. RESULTS: The greater sensitization was to D. pteronyssinus (36,9%), followed by D. siboney (35%) and B. tropicalis (33%). The greater geometric mean of the wheal diameter was 5,14 mm for D. pteronyssinus (IC95%: 4.52-5.76 mm); 4.82 mm for D. siboney (IC95%: 4.22-5.43 mm) and 4.25 mm for B. tropicalis (IC95%: 3.93-4.58 mm). Fifty six children (54.3%) were not sensitive to none of the three mites. In 45.7% we found sensitization at least to one mite, and 21.4% were sensitive to the three mites. There were no significant differences (p >0.05) in the sensitization according to sex, place of residence and degree of exposure to house dust. The percentage of sensitive patients with rhinitis plus asthma was more significant (p < 0.001), and in them, the geometric mean of the wheal diameter was significant for D. pteronyssinus (p=0.028) and D. siboney (p=0. 027). CONCLUSIONS: A third of our studied child population, residing in a non-industrialized tropical area, presented sensitization to one or some of the three tested mites. There was a different pattern of sensitization with mites in relation to gender. Patients with asthma plus rhinitis showed more sensitization concerning the number and intensity of the skin tests.