Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis.

BACKGROUND: The safety and efficacy of an attenuated G1P[8] human rotavirus (HRV) vaccine were tested in a randomized, double-blind, phase 3 trial. METHODS: We studied 63,225 healthy infants from 11 Latin American countries and Finland who received two oral doses of either the HRV vaccine (31,673 infants) or placebo (31,552 infants) at approximately two months and four months of age. Severe gastroenteritis episodes were identified by active surveillance. The severity of disease was graded with the use of the 20-point Vesikari scale. Vaccine efficacy was evaluated in a subgroup of 20,169 infants (10,159 vaccinees and 10,010 placebo recipients). RESULTS: The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85 percent (P<0.001 for the comparison with placebo) and reached 100 percent against more severe rotavirus gastroenteritis. Hospitalization for diarrhea of any cause was reduced by 42 percent (95 percent confidence interval, 29 to 53 percent; P<0.001). During the 31-day window after each dose, six vaccine recipients and seven placebo recipients had definite intussusception (difference in risk, -0.32 per 10,000 infants; 95 percent confidence interval, -2.91 to 2.18; P=0.78). CONCLUSIONS: Two oral doses of the live attenuated G1P[8] HRV vaccine were highly efficacious in protecting infants against severe rotavirus gastroenteritis, significantly reduced the rate of severe gastroenteritis from any cause, and were not associated with an increased risk of intussusception. (ClinicalTrials.gov numbers, NCT00139347 and NCT00263666.)

Severity and age of rotavirus diarrhea, but not socioeconomic conditions, are associated with rotavirus seasonality in Venezuela.

Rotavirus (RV) epidemiology presents differences between developing and developed countries among which are seasonality, age at first infection, variability of strain in circulation and severity of disease. Since, in Venezuela, we have distinct seasonal patterns of RV occurrence, we examined the epidemiological profile of RV disease associated to these differences by analyzing data from previous studies conducted in Venezuela. Data were collected from children <5 years of age with diarrhea seen in six hospitals located in five cities. Socio-demographic and clinical characteristics of RV illness were analyzed according to RV identification by ELISA assay and the seasonal patterns of RV circulation (marked versus minimal seasonality). A total of 6,742 episodes of diarrhea (1,820 rotavirus positive and 4,922 rotavirus negative) were evaluated: 1,951 in Caracas, Cumaná and Pto. Ordaz (minimal seasonality) and 4,791 in Mérida and Valencia (marked seasonality). Mean age (months) of children with RV was 8.14 +/- 6.74 and 12.21 +/- 9.62 (P < 0.0001) in areas with minimal and marked seasonality, respectively. RV disease was more frequent (33% vs. 24%; OR = 1.536; 95% CI: 1.36-1.73), more severe (dehydration: 64% vs. 29%; OR = 4.436; 95% CI: 3.61-5.44) and more common in infants than in older children (79% vs. 60%; OR = 2.521; 95% CI: 2.01-3.14) in cities with minimal seasonality than in those with marked seasonality. Socioeconomic conditions were not associated with seasonality. In environments with minimal seasonality, children are infected with RV at younger ages and the disease is more severe regardless of malnutrition and poverty.

Rotavirus mortality confirmed by etiologic identification in Venezuelan children with diarrhea.

BACKGROUND: Hospital-based studies to determine the etiology of deaths from diarrhea are scarce. In this study, we specifically analyzed deaths due to rotavirus to assess the rotavirus impact on diarrhea mortality. METHODS: To determine the rotavirus proportion contributing to mortality due to diarrhea, we analyzed data obtained from a hospital-based mortality surveillance, conducted over 7 years, in the Ciudad Hospitalaria Dr. Enrique Tejera, Valencia, Venezuela. Rotavirus was identified in stool samples collected from children who died of diarrhea, by a confirmatory ELISA and/or reverse transcription polymerase chain reaction. RESULTS: Our results show that rotavirus (21%; 21/100) is the leading cause of death due to diarrhea among children <5 years of age; rotavirus also has an important impact (2%; 21/1336) on deaths from all causes in this age group. Shigella spp. (19%; 13/69) was the second most important cause of death, followed by calicivirus (6%; 3/53). Furthermore, this study documents a seasonal pattern in the deaths due to rotavirus (odds ratio 3.28; 95% confidence interval 1.13-9.76). CONCLUSIONS: For Venezuela, it is estimated that approximately 300 children <5 years of age die of rotavirus each year, which means that 1 in 1800 children die by the age of 5. Rotavirus was found to be the main cause of death due to diarrhea, which supports previous estimations. This is the first study to present data of cause-specific mortality due to diarrhea based on hospital surveillance of diarrhea etiologies.

Evaluation of safety, immunogenicity and efficacy of an attenuated rotavirus vaccine, RIX4414: A randomized, placebo-controlled trial in Latin American infants.

BACKGROUND: A live attenuated monovalent rotavirus vaccine RIX4414 was developed with a human strain of G1P1A P[8] specificity to reduce the rotavirus burden in children. METHODS: A double blind, randomized, placebo-controlled study evaluated the efficacy, immunogenicity, safety and reactogenicity of 2 oral doses of RIX4414 (10(4.7), 10(5.2) or 10(5.8) focus-forming units) at 2 and 4 months coadministered with routine vaccinations and oral poliovirus vaccine given for study purposes at least 14 days apart. The 2155 infants (1618 vaccine/537 placebo) enrolled in Brazil, Mexico and Venezuela were followed until 1 year of age. RESULTS: Antirotavirus IgA seroconversion rates 2 months after dose 2 ranged between 61% (10(4.7) ffu group) and 65% (10(5.8) ffu group), and most of the infants had seroprotective levels of antibodies to coadministered routine vaccinations. The reactogenicity profile of RIX4414 was similar to that of the placebo, and no vaccination-related serious adverse events were reported. Protective efficacy against severe and any rotavirus gastroenteritis from 15 days post-dose 2 was highest in the 10(5.8) ffu group [86%; 95% confidence interval (95% CI), 63-96% and 70% (95% CI 46-84%), P < 0.001, 2-sided Fisher's exact test]. The efficacy against hospitalization was 79% (95% CI 48-92%) for pooled vaccine groups. Multiple rotavirus serotypes [G1 (50%), G9 (40%), G2, G3 and G4] were identified from gastroenteritis stools (enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction) during the study period. For severe gastroenteritis caused by G9 serotypes, the protection reached 77% (95% CI 18-96%) in the 10(5.8) ffu group, providing proof of concept that the monovalent G1P1A P[8] human rotavirus vaccine elicits cross-protection against the G9 strain. A reduction in any and severe rotavirus gastroenteritis was already observed at post-dose 1 (period: day of dose 1 to 14 days post-dose 2) in vaccinees compared with placebo recipients. CONCLUSIONS: Two doses of RIX4414 are highly efficacious, providing cross-protection (G1 and G9 strains, prevalent during this study) and early protection against any and severe rotavirus gastroenteritis and hospitalization to infants in Latin America.

Epidemiologic and clinical characteristics of rotavirus disease during five years of surveillance in Venezuela.

BACKGROUND: To effectively introduce a rotavirus vaccine in developing countries, it is necessary to estimate the burden of rotavirus disease. Therefore we examined the epidemiologic and clinical features of rotavirus diarrhea in children younger than 5 years of age in Carabobo State and extrapolated these results to the rest of Venezuela. METHODS: From January 1, 1998 to December 31, 2002, we conducted surveillance for rotavirus diarrhea in all children younger than 5 years of age at the Ciudad Hospitalaria Dr Enrique Tejera, in Valencia (Carabobo). RESULTS: Rotavirus is the major cause of diarrhea in children younger than 5 years of age in Venezuela, accounting for one-fourth (23%) of all episodes of diarrhea requiring medical treatment and one-third (33%) of those requiring hospitalization. Rotavirus diarrhea was responsible for 3% of all hospitalizations and 2% of all medical visits. In Valencia, rotavirus had a marked seasonal peak during the dry and cold months of the year. Rotavirus was most frequent in children 3-23 months of age, and 61% of the cases occurred by the age of 1 year. In addition, rotavirus diarrhea was more severe in younger children. Overall, by the age of 5 years, 1 child in 72 will be hospitalized and 1 in 24 will visit the clinic for rotavirus disease. In Venezuela, we estimated that each year, 118,000 children experience rotavirus illness requiring medical care and 39,000 children require hospitalization. CONCLUSIONS: This study confirms the significant impact of rotavirus disease in Venezuela. Rotavirus vaccines currently in development could diminish the morbidity associated with this common cause of childhood diarrheal disease.

Intussusception-associated hospitalization among Venezuelan infants during 1998 through 2001: anticipating rotavirus vaccines.

BACKGROUND: The first licensed rotavirus vaccine was withdrawn from use in the United States because of a low risk of intussusception. Consequently tests of new rotavirus vaccines will require some baseline knowledge of the rates and treatment of intussusception in countries where these vaccines will be tested. Therefore the objective of this study was to assess hospitalization rates and describe the epidemiologic and clinical characteristics of intussusception in Carabobo, Venezuela. METHODS: This study reviewed hospital data and clinical records of pediatric patients with intussusception admitted to eight hospitals in Carabobo between January 1, 1998 and December 31, 2001. RESULTS: For the 4-year period the average annual hospitalization rate for intussusception among infants (<1 year old) in Carabobo was 35 per 100 000 infants per year (range, 22 to 44), and intussusception was more common among boys (58 per 100 000 infants per year) than girls (29 per 100 000 infants per year) (P = 0.006). One of 67 cases occurred in the first 3 months of life (0 to 2), 55% (37) patients were 3 to 5 months old, 31% (21) were 6 to 11 months old and 12% (8) were > or =12 months old. Surgical reduction was required in 88% (52 of 59) of infants but only 1 required bowel resection. The monthly distribution of intussusception-associated hospitalizations showed no consistent seasonal pattern with the seasonality observed for patients hospitalized with rotavirus disease. CONCLUSIONS: This study provides some data about the incidence of intussusception and its epidemiology in a developing country where current or future field trials with rotavirus vaccine will be conducted.

A rotavirus vaccine for prophylaxis of infants against rotavirus gastroenteritis.

The need for safe and effective vaccines to reduce morbidity and mortality caused by rotavirus gastroenteritis in children is well-known. A live attenuated monovalent rotavirus vaccine (Rotarix) containing human rotavirus strain RIX4414 of G1P1A P[8] specificity is being developed to meet the global need. An overview of RIX4414 trials in developed and developing settings is presented for 3 selected trials conducted in Finland (pilot study), Latin America (Brazil, Mexico and Venezuela) and Singapore involving 5024 infants. The vaccine was well-tolerated, with no increase in any solicited symptoms as compared with the placebo. After 2 doses, 61-91% of vaccinated infants developed rotavirus-specific IgA antibodies. There was no interference with immunogenicity of coadministered routine pediatric vaccines. Rotarix significantly reduced rotavirus gastroenteritis episodes and rotavirus-related hospitalizations in vaccinated infants compared with placebo recipients (P < 0.05). Vaccine efficacy was observed against severe rotavirus gastroenteritis caused by G1 and non-G1 types including the emerging G9 type (P < 0.05) in Latin America. These results show prospects for widespread use of Rotarix to reduce rotavirus disease burden and warrant continued worldwide evaluation.

La revista Salus durante los años 2010 - 2015 / The Salus magazine during the years 2010 - 2015

Este artículo caracteriza el proceso de gestión editorial llevado a cabo durante el período comprendido entre el año 2010 hasta el 2015 en la Revista Salus. Con el mismo se pretende dar a conocer no sólo el alcance de esta gestión, sino también la producción de artículos científicos publicados en la revista, como órgano de divulgación científica multidisciplinaria, editado por la Facultad de Ciencias de la Salud de la Universidad de Carabobo, Valencia - Venezuela. Actualmente la revista Salus se publica en formatos impreso y electrónico, con visibilidad internacional y libre acceso a través de repositorios internacionales y nacionales. Este trabajo realiza una descripción detallada del flujo editorial utilizado por la revista y al que se someten los artículos enviados a la misma. Los resultados muestran que tipos de manuscritos se publican, cuántos son recibidos y tramitados, así como el tiempo promedio de duración del arbitraje y de todo el proceso editorial. Con este manuscrito se deja constancia de los años de gestión citados, donde se ha trabajado para mejorar la calidad científica, distribución y difusión de la Revista Salus, tal como exige el nivel actual nacional y latinoamericano. Sin embargo, queda mucho por hacer, por mejorar y por continuar. Como producto de la evaluación que se genera del presente trabajo, surge como propuesta, adscribirse o diseñar un sistema automatizado de gestión editorial que, sin duda alguna, contribuirá a la esperada profesionalización de la edición científica.

This article discusses the editorial management process carried out during the period from 2010 to 2015 in the journal Salus. The aim is to inform not only the scope of this effort, but also the production of scientific papers published in the journal, as a body of multidisciplinary scientific publication, reproduced by the Faculty of Health Sciences at the University of Carabobo, Valencia - Venezuela. Currently, Salus is published in print and electronic formats, with international visibility and free access by international and national repositories. This paper makes a detailed description of the editorial workflow used by the journal and the process of the papers submitted to the journal. The results show what kind of manuscripts are published, how many are received and processed, the average timeline of the evaluation and the entire editorial process. This manuscript records the years of editorial management, in which worked has done to improve the scientific quality, distribution and diffusion of Salus, as required by national and Latin American current level. However, much remains to be done, and continue to improve. As a result of the evaluation of this work, it emerges a proposal of the design of an automated editorial management system that will undoubtedly contribute to the expected professionalization of scientific publishing.

Síncope vasovagal en pacientes pediátricos / Vasovagal syncope in pediatric patients

La finalidad de este estudio fue caracterizar clínica y epidemiológicamente el síncope vasovagal en pacientes pediátricos que acudieron a la consulta externa de cardiología del Hospital de Niños "Dr. Jorge Lizarraga" de la Ciudad Hospitalaria "Dr. Enrique Tejera". Valencia Estado Carabobo, en el período Enero-Agosto 2012. Se realizó un estudio de tipo descriptivo, no experimental, transversal. La población estuvo constituida por 66 pacientes pediátricos que reunieron los siguientes criterios de inclusión: edades comprendidas entre el primer día de vida y los 18 años de edad y con diagnóstico de síncope vasovagal. Se realizó revisión documental de las historias clínicas; dicha información fue recolectada mediante un instrumento tipo ficha clínica diseñada por los investigadores. Los resultados se representaron en frecuencia absoluta, relativa y se realizaron comparaciones de proporciones asumiendo un nivel de significancia de P<0,05 mediante el programa Statistics versión 8. En los resultados 63,63% (P< 0,01) fueron del sexo femenino, el síncope vasovagal prevaleció en la edad escolar con 43,93%. La bipedestación prolongada constituyó el factor desencadenante principal. El síntoma prodrómico más frecuente fue mareo 31,11%. De los mecanismos fisiopatológicos, el tipo vasodepresor predominó con 53,03%. En 48% de los pacientes la frecuencia de aparición de los síntomas fue mensual.

The purpose of this study was to determine the clinical and epidemiological characterization of the vasovagal syncope in pediatric patients attending the outpatient cardiology practice at "Dr. Jorge Lizarraga" Children’s Hospital in "Dr. Enrique Tejera" Hospital City. Valencia, Carabobo state, between January - August 2012. A non-experimental, cross-sectional, descriptive study was done. The population consisted of 66 pediatric patients that gathered the following inclusion criteria: ages between one day of being born and 18 years old and with vasovagal syncope diagnose. A documentary review of the medical records was made; the information was collected with an instrument designed by the investigators similar to medical records. The results were presented in absolute and relative frequency and proportion comparisons were made assuming a significance level of p<0,05 using the program Statistix version 8. 63,63% were females, and school age was predominant with vasovagal syncope 43,93%. Prolonged bipedalism was the main triggering factor. The more frequent prodromal symptom was sickness with 31,11%. Pathophysiological mechanisms vasodepressor type predominated with 53.03%. The symptoms appeared monthly in 48% of the population.

Actitud de las madres en el cumplimiento del calendario de vacunación de niños menores de 6 años / Attitude of mothers regarding compliance with vaccination calendar

La finalidad de este estudio fue determinar la actitud de las madres hacia el cumplimiento del calendario de vacunación de niños menores de 6 años en el servicio de hospitalización del hospital de niños Dr. Jorge Lizarraga, en Valencia, Estado Carabobo. Fue un estudio transversal, descriptivo, no experimental; se aplicó una encuesta, previa validación y consentimiento informado a 71 madres. Los datos fueron tabulados y graficados mostrándose frecuencias absolutas y porcentajes. En los resultados se determinó que 94,4 % de las madres manifestó conocer el calendario de vacunas; 43% negó haber visto o escuchado mensajes sobre vacunación en el último mes; 40,8% desconoce la presencia de nuevas vacunas; 47,9% tiene la creencia de que las vacunas curan enfermedades en sus niños; 25,4% tiene creencias acerca de falsas contraindicaciones en la aplicación de vacunas; 56,3% ha presentado retraso en el cumplimiento de la dosis de alguna vacuna; 97,2% de las madres afirmó que deberían haber más centros de vacunación. En conclusión, se demostró que las madres refieren tener conocimiento acerca del calendario de inmunizaciones de sus hijos; así mismo, se observó falta de información a través de mensajes y/o programas educativos que reciben las madres y desconocimiento de éstas sobre nuevas inmunizaciones. Las madres presentan retraso en el cumplimiento de las vacunas de sus niños. Es necesario reforzar los procesos de educación y promoción de las vacunas, así como también crear más centros de vacunación.

The purpose of this study was to determine the attitude of mothers regarding compliance with the vaccination calendar of children less than 6 years of age in the pediatrics hospitalization service at the children hospital Dr. Jorge Lizarraga, in Valencia, Carabobo State. This was a descriptive cross-sectional, non-experimental study. A survey designed by the author was applied, after validation and informed consent to 71 mothers. The data was displayed in graphs and tabulated showing absolute frequencies and percentage. Results indicated that 94.4% of the mothers was aware of the calendar of vaccines; 43.0% denied having seen or heard messages on vaccination in the last month, at the time of the survey; 40.8% did not know the existence of new vaccines. Also, 47.9% had the belief that vaccines would cure diseases in their children. 25.4% had beliefs about false contraindications in the application of vaccines. 56.3% of the mothers were late at complying with the dose of some vaccine; 97.2% thought that more vaccination centers need to be created. In conclusion, it was shown that mothers are aware of the immunizations calendar of their children; also, a lack of information through educational messages and/or programs that the mothers receive was observed, as well as ignorance of the mothers on the existence of new immunizations. Mothers are late at complying with their children’s vaccines. It is necessary to reinforce the educational process on this issue, as well as the promotion of vaccines. Also, more vaccination centers need to be created.

Efficacy of the human rotavirus vaccine RIX4414 in malnourished children.

UNLABELLED: The effect of nutritional status on protective efficacy of a live attenuated human rotavirus vaccine (RIX4414) was studied. Vaccine protection was evaluated through a secondary analysis of data from an efficacy study conducted in Brazil, Mexico, and Venezuela. Vaccine efficacy against rotavirus gastroenteritis (RVGE) was similar in well-nourished and malnourished infants: 74.1% (95% confidence interval [CI], 52.2%-86.2%) and 73% (95% CI, 11.2%-92.3%) for severe RVGE and 60.9% (95% CI, 37.4%-75.4%) and 61.2% (95% CI, 10.4%-83.1%) for RVGE of any severity, respectively. RIX4414 significantly decreased the rate of RVGE regardless of nutritional status, which suggests that this patient group can also benefit from rotavirus vaccination. CLINICAL TRIALS REGISTRY: e-Track 444563-006, NCT00385320 (http://www.clinicaltrials.gov).

Serotipos y resistencia antimicrobiana de cepas de Shigella flexneri aisladas de niños con diarrea aguda: Relación entre el serotipo y la severidad del episodio / Serotype and antimicrobial resistance of Shigella flexneri strains isolated from children with acute diarrhea: Relationship between serotype and severity of the episode

Se determinó el serotipo, susceptibilidad a los antimicrobianos y la relación de severidad de la infección con el serotipo, a un grupo de 50 cepas de S. flexneri aisladas de niños menores de 5 años con diarrea: 25 niños deshidratados y 25 no deshidratados. Para la tipificación se utilizaron antisueros comerciales y la susceptibilidad a los antimicrobianos se realizó por el método de difusión en disco. Características epidemiológicas y clínicas de los episodios: media de edad 13,32 meses ± 12, clase obrera y marginal 94% (P< 0,05), eutróficos 80% (P<0,05), sangre macroscópica en heces 82% (P< 0,05), vómitos 60% (P> 0,05). El serotipo con mayor frecuencia fue el 2a (40%), seguido por el 3a (24%), 2b (18%), 1a (6%), 6 (4%), 3b (2%), 4a (2%), variante “X” (2%) y variante “Y” (2%). El mayor porcentaje de resistencia se observó a tetraciclina (96%), seguido por ampicilina (94%), cloranfenicol (90%), amoxicilina ácido clavulánico (84%) y trimetoprin-sulfametoxazol (72%). La desnutrición (36%, P< 0,05) y el serotipo 2a (56%, P< 0,05) se observaron con mayor frecuencia en los niños deshidratados, mientras que el serotipo 2b predominó en los no deshidratados (32%, P< 0,05). La prevalencia del serotipo 2a, su asociación con la severidad del episodio y la elevada resistencia a los antibióticos alertan sobre la problemática de la infección por Shigella en el país y refuerza la necesidad de estudios para ajustar pautas en el tratamiento.

Serotype, antimicrobial susceptibility, and severity of the infection according to serotype, were determined in a group of 50 Shigella flexneri strains isolated from children less than 5 years old with diarrhea: 25 children dehydrated and 25 non dehydrated. Commercial antisera were used for serotyping and antimicrobial susceptibility was determined by the disc diffusion method. Clinical and epidemiological characteristics of the episodes: mean age 13.22 ± 12 months; 94% belonged to laborer and marginal classes (P<0.05); 80% eutrophic (P<0.05); 82% macroscopic blood in feces (P<0.05); 60% vomits (P>0.05). The most frequent serotype was 2a (40%), followed by 3a (24%), 2b (18%), 1a (6%), 6 (4%), 3b (2%), 4a (2%), variant “X” (2%) and variant “Y” (2%). The highest resistance percent was found for tetracycline (96%), followed by ampicylline (94%), chloramphenicol (90%), amoxicylline clavulonic acid (84%) and trimetoprim-sulfametoxazol (72%). Malnourishment (32%, P<0.05) and serotype 2a (56%, P<0.05) were seen more frequently in dehydrated children, while serotype 2b predominated in non dehydrated children (32%, P<0.05). Prevalence of serotype 2a and its association with the severity of the episode and high antibiotic resistance alert regarding the problem of Shigella infections in our country and reinforce the need of further studies to adjust treatment norms.

Inmunizaciones: [revisión] / Immunizations: [review]

Los avances en la prevención de la enfermedad diarreica aguda con el uso de vacunas orales están presentes gracias a las investigaciones en el área de los trabajos realizados en cólera, fiebre tifoidea y con más éxito en la prevención de la diarrea por rotavirus. en este consenso desarrollamos los elementos actualizados en la inmunización contra cólera, fiebre tifoidea, indicaciones y futuras vacunas. en especial, se hace referencia a la vacunación contra rotavirus, sus estudios iniciales, evaluación de la investigación en fase III (realizada en Venezuela), las características particulares de cada vacuna desarrollada y en uso hoy en día, su aplicación y seguimiento una vez iniciado el plan nacional de vacunación, finalizando con los estudios de impacto económico y costo-efectividad.

Advances in prevention of acute diarrheal disease with the use of oral vaccines have been accomplished thanks to research in cholera, typhoid fever and, with more success, in the prevention of rotavirus diarrhea. This consensus addresses updates in immunization against cholera, typhoid fever, indications and future vaccines. In particular, we refer to vaccinations against rotavirus, their initial studies, research evaluation in phase III (held in Venezuela), particular characteristics of each vaccine developed and in use today, and the follow up of its implementation once the national vaccination plan is initiated. Final considerations in relation to the economic impact and cost effectiveness studies are stated.