The Potential of Surveillance Data for Dengue Risk Mapping: An Evaluation of Different Approaches in Cuba.

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.

Engineered Mycobacterium tuberculosis antigen assembly into core-shell nanobeads for diagnosis of tuberculosis.

Despite recent advances in diagnosis, tuberculosis (TB) remains one of the ten leading causes of death worldwide. Here, we engineered Mycobacterium tuberculosis (Mtb) proteins (ESAT6, CFP10, and MTB7.7) to self-assemble into core-shell nanobeads for enhanced TB diagnosis. Respective purified Mtb antigen-coated polyester beads were characterized and their functionality in TB diagnosis was tested in whole blood cytokine release assays. Sensitivity and specificity were studied in 11 pulmonary TB patients (PTB) and 26 healthy individuals composed of 14 Tuberculin Skin Test negative (TSTn) and 12 TST positive (TSTp). The production of 6 cytokines was determined (IFNγ, IP10, IL2, TNFα, CCL3, and CCL11). To differentiate PTB from healthy individuals (TSTp + TSTn), the best individual cytokines were IL2 and CCL11 (>80% sensitivity and specificity) and the best combination was IP10 + IL2 (>90% sensitivity and specificity). We describe an innovative approach using full-length antigens attached to biopolyester nanobeads enabling sensitive and specific detection of human TB.

Microbial biodiversity in the throats of pulmonary tuberculosis patients and tuberculin skin test (TST) positive and negative healthy individuals in Malaysia.

The purpose of this study was to investigate the composition of throat microbiota in pulmonary tuberculosis patients (PTB) in comparison to healthy tuberculin skin test positive (TSTp) and negative (TSTn) individuals. Throat swabs samples were collected, and the microbiota was characterized. Richer operational taxonomic units (OTUs) were present in PTB group, compared to TSTp and TSTn. Regarding alpha diversity analysis there was a higher community diversity in TSTn compared to TSTp. Beta diversity analysis showed different species composition in TSTp compared to TSTn and PTB. There was higher presence of Firmicutes in PTB and TSTn compared to TSTp group at phylum level. At the genus level, Leuconostoc and Enterococcus were higher in TSTn compared to TSTp and Pediococcus, Chryseobacterium, Bifidobacterium, Butyrivibrio, and Bulleidia were higher in PTB compared to TSTn. Streptococcus was higher in TSTn compared to PTB and Lactobacillus in PTB compared to TSTp. At species level, Streptococcus sobrinus and Bulleidia moorei were higher in PTB compared to TSTn individuals, while Lactobacillus salivarius was higher in PTB compared to TSTp. The differences in the microbiome composition could influence the resistance/susceptibility to Mtb infection.

The additional benefit of residual spraying and insecticide-treated curtains for dengue control over current best practice in Cuba: Evaluation of disease incidence in a cluster randomized trial in a low burden setting with intensive routine control.

BACKGROUND: Aedes control interventions are considered the cornerstone of dengue control programmes, but there is scarce evidence on their effect on disease. We set-up a cluster randomized controlled trial in Santiago de Cuba to evaluate the entomological and epidemiological effectiveness of periodical intra- and peri-domiciliary residual insecticide (deltamethrin) treatment (RIT) and long lasting insecticide treated curtains (ITC). METHODOLOGY/PRINCIPAL FINDINGS: Sixty three clusters (around 250 households each) were randomly allocated to two intervention (RIT and ITC) and one control arm. Routine Aedes control activities (entomological surveillance, source reduction, selective adulticiding, health education) were applied in the whole study area. The outcome measures were clinical dengue case incidence and immature Aedes infestation. Effectiveness of tools was evaluated using a generalized linear regression model with a negative binomial link function. Despite significant reduction in Aedes indices (Rate Ratio (RR) 0.54 (95%CI 0.32-0.89) in the first month after RIT, the effect faded out over time and dengue incidence was not reduced. Overall, in this setting there was no protective effect of RIT or ITC over routine in the 17months intervention period, with for house index RR of 1.16 (95%CI 0.96-1.40) and 1.25 (95%CI 1.03-1.50) and for dengue incidence RR of 1.43 (95%CI 1.08-1.90) and 0.96 (95%CI 0.72-1.28) respectively. The monthly dengue incidence rate (IR) at cluster level was best explained by epidemic periods (Incidence Rate Ratio (IRR) 5.50 (95%CI 4.14-7.31)), the IR in bordering houseblocks (IRR 1.03 (95%CI 1.02-1.04)) and the IR pre-intervention (IRR 1.02 (95%CI 1.00-1.04)). CONCLUSIONS: Adding RIT to an intensive routine Aedes control programme has a transient effect on the already moderate low entomological infestation levels, while ITC did not have any effect. For both interventions, we didn't evidence impact on disease incidence. Further studies are needed to evaluate impact in settings with high Aedes infestation and arbovirus case load.

Prevalence of Pneumococcal Nasopharyngeal Carriage Among Children 2-18 Months of Age: Baseline Study Pre Introduction of Pneumococcal Vaccination in Cuba.

BACKGROUND: A new vaccine candidate against pneumococcus is being developed in Cuba, and it is a priority of the national health system. There is limited information on nasopharyngeal colonization burden, though it is essential for monitoring the impact of the vaccine. The study aims to estimate the prevalence of nasopharyngeal colonization in children 2-18 months of age and identify circulating serotypes, antimicrobial resistance and its association with selected risk factors. METHODS: A cross-sectional study was conducted between October and December 2013 in Cienfuegos municipality. Inclusion criteria were evaluated, and informed consent was obtained from the parents. Clinical and epidemiologic data were collected through a semistructured questionnaire. Nasopharyngeal swabs according to established protocols were taken. Data analysis included frequency distributions and comparison of proportions. The association between colonization and selected risk factors was assessed by multivariate analysis. RESULTS: A total of 984 children (87.2% living in urban areas) were included. The overall prevalence of colonization was 21.6%. The most frequent serotypes isolated were 6A (23.1%), 23F (10.8%), 6B (10.3%), 19F (8.5%) and 14 (3.3%). We found no resistance to ß-lactamases in circulating serotypes. Living with sibling younger than 5 years, previous respiratory infections, previous hospitalization and day-care attendance were determinants of nasopharyngeal carriage. CONCLUSIONS: The findings suggest that the burden of pneumococcal disease and colonization in Cuba could be significantly affected after vaccine introduction.

Safety and Immunogenicity of Cuban Antipneumococcal Conjugate Vaccine PCV7-TT in Healthy Adults.

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 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. KEYWORDS Invasive pneumococcal diseases, pneumococcal vaccines, conjugate vaccines, immunization, randomized clinical trial, safety, Cuba.

In Silico identification of M. TB proteins with diagnostic potential.

TB, caused by Mycobacterium tuberculosis (MTB), is one of the major global infectious diseases. For the pandemic control, early diagnosis with sensitive and specific methods is fundamental. With the advent of bioinformatics' tools, the identification of several proteins involved in the pathogenesis of TB (TB) has been possible. In the present work, the MTB genome was explored to look for molecules with possible antigenic properties for their evaluation as part of new generation diagnostic kits based on the release of cytokines. Seven proteins from the MTB proteome and some of their combinations suited the computational test and the results suggested their potential use for the diagnosis of infection in the following population groups: Cuba, Mexico, Malaysia and sub-Saharan Africa. Our predictions were performed using public bioinformatics tools plus three computer programs, developed by our group, to facilitate information retrieval and processing.

In silico identification of common epitopes from pathogenic mycobacteria.

An in silico study was carried out to identify antigens for their possible collective use as vaccine candidates against diseases caused by different classes of pathogenic mycobacteria with significant clinical relevance. The genome sequences of the relevant causative agents were used in order to search for orthologous genes among them. Bioinformatics tools permitted us to identify several conserved sequences with 100% identity with no possibility of cross-reactivity to the normal flora and human proteins. Nine different proteins were characterized using the strain H37Rv as reference and taking into account their functional category, their in vivo expression and subcellular location. T and B cell epitopes were identified in the selected sequences. Theoretical prediction of population coverage was calculated for individual epitopes as well as their combinations. Several identical sequences, belonging to six proteins containing T and B cell epitopes which are not present in selected microorganisms of the normal microbial flora or in human proteins were obtained.

Vigilancia de eventos adversos de la vacuna plisacárida meningocócica A y C durante una campaña de vacunación en Níger / Adverse event surveillance of the polysaccharide meningococcal A and C vaccine during a vaccination campaign in Niger

La inmunoprofilaxis constituye la estrategia por excelencia para la prevención y control de las epidemias de meningitis meningocócica provocadas por el serogrupo A de Neisseria meningitidis en el llamado cinturón de la meningitis en África, donde alcanza altas tasas de morbimortalidad. La vacuna liofilizada de polisacáridos purificados de Neisseria meningitidis de los serogrupos A y C fue producida como resultado de un convenio de colaboración entre el Instituto Finlay, Centro de Investigación, Desarrollo y Producción de Vacunas de Cuba y el Instituto de Tecnología e Inmunobiológicos de Bio-Manguinhos de Brasil, a solicitud de la Organización Mundial de la Salud, para cubrir las necesidades de la vacuna en los países africanos en emergencia sanitaria. Durante la campaña de vacunación desarrollada contra un brote epidémico en Níger, en el 2009, se realizó un estudio de vigilancia poslicenciamiento, con el objetivo de describir los eventos adversos consecutivos a la administración de este producto a 303.037 personas. Se utilizaron dos métodos para la recolección de los eventos adversos: notificación espontánea y vigilancia intensiva en los hospitales. Se reportaron un total de 81 eventos adversos, de los cuales solo el 11% fueron categorizados "inducidos por la vacuna" y considerados "muy probablemente relacionados" con esta. Los resultados obtenidos muestran que la vacuna utilizada en la campaña de vacunación de Níger es segura y poco reactogénica y el perfil de seguridad se corresponde con el descrito en el registro sanitario de Brasil(AU)

Immunoprophylaxis is the choice strategy for the prevention and control of meningococcal meningitis epidemics caused by Neisseria meningitidis serogroup A in the so-called meningitis belt of Africa, a disease that reaches high rates of morbidity and mortality. The lyophilized purified polysaccharide vaccine from Neisseria meningitidis serogroups A and C was produced as a result of a collaboration agreement between Finlay Institute, Center for Research, Development and Production of Vaccines, Cuba and the Institute of Technology and Bio-Immunobiologicals Manguinhos of Brazil, at the request of the World Health Organization to meet the needs of the vaccine in African countries in health emergencies. In the vaccination campaign carried out during an outbreak in Niger in 2009, a study of pharmacovigilance was conducted to describe the adverse events following the administration of this product to 303 037 people. Two methods were used to collect adverse events (spontaneous reporting and intensive search in hospitals). A total of 81 adverse events were reported, only 11% were under the category «induced by the vaccine¼ and considered «very probably related¼ to this. The results show that the vaccine used in the immunization campaign in Niger is safe, has low reactogenicity and their safety profile corresponds to that described in the sanitary medical registry in Brazil(AU)

Portadores nasofaríngeos de Neisseria meningitidis en trabajadores con riesgo ocupacional / Nasopharyngeal carriers of Neisseria meningitidis in workers with occupational risk

Los portadores de Neisseria meningitidis constituyen la principal fuente de infección y transmisión de la enfermedad meningocócica. Conocer su prevalencia, las características de las cepas aisladas y los factores de riesgos asociados con el estado de portador, aportan datos valiosos al control y vigilancia epidemiológica de esta entidad clínica. Para cumplimentar los objetivos propuestos se realizó un estudio transversal descriptivo de portadores de N meningitidis en 112 trabajadores de un centro de producción de biofarmacéuticos de La Habana, con edades comprendidas entre 18_60 años. Previo a su realización se cumplió con las exigencias bioéticas requeridas para este tipo de estudio. A todos se les realizó un exudado nasofaríngeo y una encuesta, donde se indagó sobre factores de riesgo (edad, sexo, hacinamiento, hàbito de fumar, consumo de bebidas alcohólicas, amigdalectomía y antecedentes de infección respiratoria) que favorecen la condición del portador. La identificación de las cepas de N meningitidis se realizó según métodos convencionales, la clasificación de los serogrupos se hizo por aglutinación en làminas portaobjetos con antisueros comerciales y para la identificación de los serotipos y subtipos se empleó un ensayo inmunoenzimàtico (ELISA) de células enteras con anticuerpos monoclonales. Se detectó un 8 por ciento de portadores de N meningitidis con predominio del serogrupo B (77,8 por ciento) y el fenotipo màs frecuente fue el B:4:P1.4 (33,3 por ciento). Al analizar el estado de portador y su asociación con los factores de riesgo, la edad (p = 0,05) y el sexo (p = 0,013) mostraron diferencias significativas. Se demostró la posibilidad del riesgo ocupacional en aquellos individuos que por su profesión estàn en contacto con microorganismos patógenos(AU)

Neisseria meningitidis carriers are the main infection and transmission source of the meningococcal disease. To know their prevalence, the characteristics of isolated strains and the risk factors associated to carrier status, provide important information for epidemiological surveillance and control. A descriptive-transversal study on N. meningitidis carriers was performed. It involved 112 workers from a biopharmaceutical production center in Havana, from 18 to 60 years old. Bioethical requirements were complied before starting the study. A nasopharyngeal swab was performed to all subjects and they were surveyed to find out on risk factors (age, sex, overcrowding, smoking and drinking habit, amygdalectomy and background of respiratory infection) that may favor the condition of the carrier. The identification of N meningitidis strains was carried out using conventional methods, the classification of the serogroups by slide agglutination with commercial antisera and the identification of serotypes and subtypes by an immunoenzymatic assay (ELISA) of whole cells with monoclonal antibodies. Eight percent of N meningitidis carriers was detected, serogroup B (77.8 percent) was predominant and B:4:P1.4 (33.3 percent) was the most frequently observed phenotype. When analyzing the carrier status and its association to risk factors, statistically significant difference was only observed in age (p=0.05) and sex (p= 0.013). The possibility of occupational risk was demonstrated in those subjects, who due to their profession are involved with pathogenic microorganisms(AU)

Randomized, double-blind, placebo-controlled trial to evaluate the safety and immunogenicity of live oral cholera vaccine 638 in Cuban adults.

A randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the safety, reactogenicity and the immunogenicity of a 2 x 10(9)CFU dose of the 638 lyophilized live attenuated cholera vaccine for oral administration, formulated and produced at Finlay Institute, City of Havana, Cuba. Thirty-six healthy female and male adult volunteers from 18 to 40 years old were involved, clinically examined and laboratory tested after the informed consent signature. Adverse events were monitored and seroconversion rates and geometrical mean titer (GMT) of vibriocidal antibodies were tested in volunteer's sera samples. Neither serious adverse events nor other damages to the volunteers due to vaccine or placebo feeding were reported during the clinical follow-up period of this study; none of the adverse events registered within the first 72 h after inoculation were life-threatening for volunteers. Neither severe nor moderate adverse events were reported. Sixty-one percent of subjects showed mild expected adverse events in an interval lower than 24h up to the first 72 h, 75% of these in the vaccinated group and 18% in the placebo group. Fourteen days after inoculation the GMT of vibriocidal antibodies in the vaccine group significantly increased in comparison to the placebo group. All subjects in the vaccine group (24) seroconverted (100%). Results show that this vaccine is safe, well tolerated and immunogenic in healthy female and male volunteers.

Ma-pi 2 macrobiotic diet intervention in adults with type 2 diabetes mellitus.

Introduction Diet is a cornerstone of comprehensive treatment of diabetes mellitus. The macrobiotic diet is low in fat and rich in dietary fiber, vegetables and whole grains, and therefore may be a good therapeutic option. Objective Assess the influence of the Ma-Pi 2 macrobiotic diet on physical, hematologic and biochemical variables, as well as on hypoglycemic medication, in adults with type 2 diabetes mellitus. Materials and Methods A 6-month dietary intervention was carried out in 16 adults with type 2 diabetes mellitus and poor glucide metabolism control (glycosylated hemoglobin, HbA1 >8.5%) receiving treatment at the Diabetic Care Center in Colón, Matanzas province, Cuba. The diet was prepared and served daily by macrobiotic specialists. Type and amount of food consumed and nutritional content were assessed using a weighted food-consumption survey. At onset and termination of the intervention, anthropometric and body composition variables were measured, as were biochemical (glucide and lipid metabolism) and other nutritional safety variables, and hypoglycemic drug use. Results The diet provided sufficient energy and protein. It was low in fat, high in complex carbohydrates and dietary fiber, and provided adequate amounts of vitamins and minerals, except for vitamin B12. At 6 months, anthropometric variables were significantly lower, lean body mass was preserved, and glucide and lipid metabolism was controlled. All participants were able to eliminate insulin treatment, and 25% continued treatment with glibenclamide only. Mean total cholesterol, LDL cholesterol and triglyceride values dropped 16.4%, 22.7% and 37.0%, respectively, while mean HDL cholesterol rose 97.8%. Mean glycemia and HbA1 values also decreased 63.8% and 54.5%, respectively. According to lipid levels and ratios, cardiovascular risk was also considerably reduced. Hemoglobin, total protein, albumin and creatinin levels indicated that nutritional safety was maintained. There were no adverse events. Conclusions In the 6-month intervention, the Ma-Pi 2 macrobiotic diet had a positive influence on weight control, body fat, and glucide and lipid metabolism in patients with type 2 diabetes mellitus. Further research is needed to validate these encouraging results, particularly a clinical trial in which a control group receives the standard diet recommended for diabetic patients.

Propuesta de un algoritmo para evaluar la causalidad de eventos adversosen los Ensayos Clínicos de Vacunas / Proposal of an algorithm to assess causality of adverse events in vaccine clinical trials

En el transcurso de los ensayos clínicos usualmente se designa a una comisión, la cual se encarga de evaluar la causalidad de los eventos adversos que se reportan y transcriben en los cuadernos de recogida de datos. Para llegar a contestar la pregunta de: ¿si una vacuna que se está estudiando ha causado un evento adverso?, los decisores pueden tomar diferentes caminos, por lo que obviamente la conclusión final podría variar mucho y la evaluación deficiente puede generar conclusiones erróneas, lo que confirma la necesidad de disponer de un procedimiento para definir lascategorías que se utilizarán para analizar y clasificar la relación de causalidad. Una forma de contestar a la pregunta es mediante la construcción de un algoritmo. En relación con los ensayos clínicos no encontramos en la literatura un algoritmo que sea el patrón clave para establecer o descartar la causalidad, sin embargo es factible diseñarlo partiendo de la metodología internacional utilizada poscomercialización, lo cual fue el propósito de este trabajo. Se diseñó una primera propuesta que fue analizada individual y colectivamente por el grupo multidisciplinario de la Gerencia Médica del Instituto Finlay. Finalmente se aprobó por consenso el algoritmo que puede ser útil para aplicar en los ensayos clínicos dentro y fuera de la institución(AU)

During clinical trials it is common to appoint a commission which is in charged of assessing the causality of adverse events which are reported and transcribed to the collection data logbooks. To be able to answer the question: Does the vaccine understudy cause an adverse event.? different pathways could be taken by decision makers, so it is obvious that the final conclusion could vary too much and a poorly assessment can generate mistaken conclusions. That confirms the need of having a procedure to define which categories must be used to analyze and to classify the relation of causality. To create an algorithm isone answer to the question. We reviewed the literature and did not find any algorithm which could be considered a master key to set or to reject causality, so this paper aims at designing an algorithm beginning with the international methodology used in post commercialization. A first proposal was designed which was individually and collectively analyzed by the multidisciplinary group of the Medical Management from Finlay Institute. Finally, the proposed algorithm was approved by consensus, which could be useful to apply in clinical trials inside and outside of the institution(AU)

Portadores de Neisseria meningitidis, caracterización de las cepas aisladas y respuesta inmune basal a VA-MENGOC-BC / Neisseria meningitidis carriers, characterization of isolated strains and basal immune response to VA-MENGOC-BC

Con el propósito de conocer la prevalencia de portadores de Neisseria meningitidis en un grupo de adolescentes, los marcadores epidemiológicos de las cepas aisladas, así como los factores de riesgo asociados con el estado de portadory la respuesta inmune basal a VA-MENGOC-BC, se realizó un estudio transversal descriptivo de portadores en 189 estudiantes de 12-19 años de un politécnico de Ciego de Ávila, siguiendo las Normas Bioéticas establecidas. A los estudiantes se les realizó un exudado faríngeo y una extracción de sangre para la obtención de suero, así como unaencuesta relacionada con aspectos de la investigación. La identificación de N meningitidis se hizo por el sistema APINH (bioMérieux). Los serosubtipos e inmunotipos se clasificaron por ELISA de células enteras con anticuerpos monoclonales y la respuesta inmune basal se detectó por el Ensayo Bactericida del Suero. Se determinó la susceptibilidad antimicrobiana de las cepas frente a la penicilina, cloranfenicol, rifampicina, sulfadiacina sódica, ceftriaxona y ciprofloxacina. La prevalencia de portadores de N meningitidis fue del 17 por ciento. Predominaron las cepas no agrupables (84,7 por ciento), seguidas por los serogrupos B (12,5 por ciento) y Z (3,1 por ciento), destacándose la ausencia del C Prevaleció el fenotipo NA:NT:P1.NST:L3,7,9 (12,5 por ciento), las cepas resistentes a la sulfadiacina (78,2 por ciento) y sensibles a penicilina(81,3 por ciento), aunque el 18,7 por ciento mostró sensibilidad intermedia a este fármaco. Al resto de los antimicrobianos todas fueron sensibles. Se constató una respuesta inmune de memoria a la vacuna antimeningocócica (VAMENGOC-BC®), 12 años después de su aplicación, con títulos bactericidas anti C y B de 25 y 42 por ciento, respectivamente, resultados que pudieran estar influenciados por la inmunización sistemática que se realiza en Cuba con esta vacuna desde 1991(AU)

A descriptive transversal study of N meningitidis carriers involving 189 students of 12-19 years old of a Polytechnic School in Ciego de Avila province was carried out. This study aimed at knowing the prevalence of N meningitidis carriers , the epidemiological markers as well as risk factors associated to carrier state and to basal immune response to VA-MENGOC-BC in teenagers. Blood sample and pharyngeal swab tests were carried out to the students, in addition a survey was performed to find out aspects of research. Identification of N meningitidis was carried out by API NH system (bioMérieux). Sero-subtypesand immunotypes were classified by whole cell ELISA with monoclonal antibodies, and basal immune response was detected by Serum Bactericidal Assay (SBA). Antimicrobial susceptibility of strains to Penicillin, Chloramphenicol, Rifampicin, SodicSulfadiazine, Ceftriaxone and Ciprofloxacine was determined. Prevalence of N meningitidis was 17 percent. Non groupable strainswere predominant (84,7 percent), followed by serogroups B (12,5 percent) and Z (3,1 percent), serogroup C was absent. PhenotypeNA:NT:P1.NST:L3,7,9 (12,5 percent) prevailed, resistant strains to sulfadiazine (78,2 percent) and sensitive to penicillin (81,3 percent), though 18,7 percent showed intermediate sensitivity to this drug. All strains were sensitive to the remaining antimicrobial drugs. Memory immune response to meningococcal vaccine (VA-MENGOC-BC) was observed , 12 years after its application, with anti C andB bactericidal titers of 25 and 42 percent respectively. We consider that these results may be influenced by systematic immunization that is carried out with this vaccine in Cuba since 1991(AU)

Elementos esenciales a considerar en los ensayos de no inferioridad / Essential elements to consider in non-inferiority studies

En algunas situaciones es común comparar una vacuna experimental con una vacuna estándar sin pretender mostrar superioridad. La hipótesis nula usual de igualdad es inapropiada y conlleva a dificultades lógicas. Con este artículo se pretende esclarecer la problemática al respecto, revisando la metodología desarrollada para estos efectos y presentando un valor conocido como límite de no inferioridad. Se discuten dos métodos para la realización de una prueba de hipótesis de no inferioridad. Se introducen además dos conceptos útiles en este tipo de estudio: preservación y descuento(AU)

Reactogenicidad e inmunogenicidad de una nueva vacuna de toxoide tetánico y diftérico con concentración reducida en adolescentes cubanos / Reactogenicity and immunogenicity of a new tetanus toxoid and reduced diphtheria toxoid vaccine in

Se realizó un estudio aleatorizado, controlado y a doble ciegas en 225 adolescentes cubanos entre 13 y 16 años de edad, con el objetivo de evaluar la reactogenicidad y la inmunogenicidad de una nueva vacuna de toxoide tetánico y toxoide diftérico con concentración reducida, producida en el Instituto Finlay, con respecto a su similar comercial IMOVAX dT adult de Aventis Pasteur. Se tomaron muestras de suero antes y 21 días después de la vacunación. La reactogenicidad de ambas vacunas fue similar. Los síntomas y signos, tanto locales como generales fueron moderados y aparecieron principalmente durante las primeras 72 h después de la vacunación. Todos los voluntarios vacunados alcanzaron niveles protectores (³0,1 UI/mL) de antitoxina contra el tétanos y la difteria. El 99,25por ciento de los inmunizados con la vacuna experimental y el 98,36por ciento de los voluntarios del grupo control presentaron niveles de antitoxina tetánica correspondientes a una protección de larga duración (³1,0 UI/mL); para la antitoxina diftérica se alcanzaron estos niveles en el 81,20por ciento y 80,33por ciento de los voluntarios en cada grupo. Los títulos medios geométricos de antitoxina tetánica (21,73 UI/mL) y antitoxina diftérica (2,55 UI/mL) inducidos por la nueva vacuna fueron superiores (p<0,05) a los del grupo control: 15,55 UI/mL y 1,84 UI/Ml, respectivamente(AU)

Estudio de inmunogenicidad de la vacuna antitifoídica cubana de / polisacárido Vi vax-TyVi® en ratones / Study of immunogenicity in mice of the Cuban Vi Polysaccharide Typhoid vaccine, vax-Tyvi

Salmonella enterica serovar Typhi es un microorganismo que provoca más de 16 millones de casos de fiebre tifoidea con aproximadamente 600 000 muertes al año en todo el mundo. Dentro de las vacunas antitifoídicas la de polisacárido capsular Vi ha encontrado, gracias a sus incuestionables ventajas, una gran aceptación entre productores y consumidores. El presente trabajo aborda el estudio de inmunogenicidad de la vacuna antitifoídica cubana de polisacárido Vi vax-TyVi‚ en ratones. El estudio estuvo conformado por un grupo control no inoculado y un segundo grupo que recibió 0,05 mL de la vacuna por vía intramuscular. Se tomaron muestras de sangre a los -3, 7, 14, 21, 28, 42, 56 y 84 días. La actividad de anticuerpos IgG antipolisacárido Vi de los sueros individuales fue determinada por ELISA. Los datos fueron analizados por grupo y por sexo y se calculó el porcentaje de seroconversión, considerándose respondedor aquel animal que al menos aumentara en cuatro veces su título inicial. La respuesta de anticuerpos inducida por la vacuna mostró un aumento notable de los títulos de IgG antipolisacárido Vi en el grupo vacunado (100 por ciento de seroconversión), mientras que el grupo control no incrementó sus niveles mínimos iniciales (0por ciento de respondedores). Aunque más dispersa, la respuesta de anticuerpos antiVi fue significativamente mayor en las hembras que en los machos(AU)

Caracterización fenotípica de cepas invasivas de Neisseria meningitidis aisladas en Cuba durante 20 años / Phenotypic characterization of invasive strains of Neisseria meningitidis isolated in Cuba during 20 years

Se investigaron los marcadores epidemiológicos (serogrupos, serotipos, subtipos, inmunotipos) de 429 cepas invasivas, aisladas en Cuba durante 20 años (1982-2002). Basándonos en el comportamiento de la incidencia de la Enfermedad Meningocócica (EM) en el período investigado, las cepas se distribuyeron en dos etapas: epidémica y postepidémica. La epidémica, comprendió 279 cepas aisladas entre 1982-1992 y la postepidémica, incluyó 150 aislamientos pertenecientes al período comprendido entre 1993-2002. Todas se cultivaron en Agar Mueller Hinton con suero fetal bovino (5(por ciento) y se incubaron 24-48 horas, 37 0C, en atmósfera húmeda con 5(por ciento) de C02. La identificación de género, especie y serogrupo, se realizó mediante métodos convencionales; para la caracterización de los sero/subtipos e inmunotipos, se utilizó el ensayo inmunoenzimático (ELISA) de células enteras con anticuerpos monoclonales. En ambas etapas predominó el serogrupo B (97,90(por ciento): epidémica (96,77(por ciento) y postepidémica (100(por ciento). Sin embargo, el serogrupo C (1,43(por ciento) y cepas no agrupables (1,8(por ciento), sólo se observaron en aislamientos de la etapa epidémica. Los otros marcadores prevalentes fueron: serotipo 4 (86,48(por ciento), subtipo P1.19,15 (78,32(por ciento), inmunotipo L3,7,9 (90,2(por ciento), todos mostraron cifras similares en ambos períodos. Predominó el fenotipo B:4:P1.19,15:L3,7,9 (69,69(por ciento), aunque, en la etapa postepidémica (77,34(por ciento), el porcentaje fue superior al de la etapa epidémica (65,66(por ciento) (p<0,05); además, en las cepas de este período, se observó una mayor diversidad de asociaciones fenotípicas. Los resultados obtenidos de esta caracterización fenotípica de las cepas de Neisseria meningitidis aisladas de enfermos aporta datos valiosos al estudio, prevención y control exitoso de la EM en Cuba(AU)

Selección de cepas atenuadas de Vibrio cholerae para la obtención de candidatos vacunales atenuados orales contra el cólera / Selection of attenuated Vibrio cholerae strains to obtain oral attenuated candidate vaccines against cholera

Se desarrolló una metodología para la selección de cepas de Vibrio cholerae O1 y O139 modificadas genéticamente, con el objetivo de obtener candidatos vacunales atenuados orales contra el cólera. A las cepas modificadas se les realizó caracterización microbiológica, susceptibilidad bacteriana y diferentes pruebas biológicas (dosis letal media, capacidad colonizadora, adherencia en ratones, intestino ligado e inoculación intraduodenal en conejos como pruebas de virulencia y potencia). Las cepas 81, 638, 638T y 1333 fueron evaluadas en ensayos clínicos para determinar su reactogenicidad e inmunogenicidad. Todas las cepas fueron sensibles a la tetraciclina y doxiclicina y mostraron su atenuación e inmunogenicidad en modelos animales, resultando las cepas 638 y 1333 inmunogénicas y no reactogénicas en voluntarios

Selección de cepas atenuadas de Vibrio cholerae para la obtención de candidatos vacunales atenuados orales contra el cólera / Selection of attenuated Vibrio cholerae strains to obtain oral attenuated candidate vaccines against cholera

Se desarrolló una metodología para la selección de cepas de Vibrio cholerae O1 y O139 modificadas genéticamente, con el objetivo de obtener candidatos vacunales atenuados orales contra el cólera. A las cepas modificadas se les realizó caracterización microbiológica, susceptibilidad bacteriana y diferentes pruebas biológicas (dosis letal media, capacidad colonizadora, adherencia en ratones, intestino ligado e inoculación intraduodenal en conejos como pruebas de virulencia y potencia). Las cepas 81, 638, 638T y 1333 fueron evaluadas en ensayos clínicos para determinar su reactogenicidad e inmunogenicidad. Todas las cepas fueron sensibles a la tetraciclina y doxiclicina y mostraron su atenuación e inmunogenicidad en modelos animales, resultando las cepas 638 y 1333 inmunogénicas y no reactogénicas en voluntarios(AU)