RESUMEN
BACKGROUND: Leptospirosis is a zoonotic disease of major importance in the tropics where the incidence peaks in rainy seasons. Natural disasters represent a big challenge to Leptospirosis prevention strategies especially in endemic regions. Vaccination is an effective option but of reduced effectiveness in emergency situations. Homeoprophylactic interventions might help to control epidemics by using highly-diluted pathogens to induce protection in a short time scale. We report the results of a very large-scale homeoprophylaxis (HP) intervention against Leptospirosis in a dangerous epidemic situation in three provinces of Cuba in 2007. METHODS: Forecast models were used to estimate possible trends of disease incidence. A homeoprophylactic formulation was prepared from dilutions of four circulating strains of Leptospirosis. This formulation was administered orally to 2.3 million persons at high risk in an epidemic in a region affected by natural disasters. The data from surveillance were used to measure the impact of the intervention by comparing with historical trends and non-intervention regions. RESULTS: After the homeoprophylactic intervention a significant decrease of the disease incidence was observed in the intervention regions. No such modifications were observed in non-intervention regions. In the intervention region the incidence of Leptospirosis fell below the historic median. This observation was independent of rainfall. CONCLUSIONS: The homeoprophylactic approach was associated with a large reduction of disease incidence and control of the epidemic. The results suggest the use of HP as a feasible tool for epidemic control, further research is warranted.
Asunto(s)
Vacunas Bacterianas/administración & dosificación , Brotes de Enfermedades/prevención & control , Homeopatía/métodos , Leptospira , Leptospirosis/epidemiología , Leptospirosis/prevención & control , Administración Oral , Estudios de Cohortes , Cuba/epidemiología , Brotes de Enfermedades/estadística & datos numéricos , Humanos , Incidencia , Leptospirosis/microbiología , Vigilancia de la Población , Estaciones del Año , Solventes , Resultado del TratamientoRESUMEN
El cólera constituye un problema de salud para muchos países en el mundo: las elevadas tasas de morbilidad y mortalidad registradas en los últimos años inquietan a la comunidad científica, pues el aumento de su incidencia podría generar una crisis global en su control. Existen factores claves en su reemergencia, entre ellos están el debilitamiento general de las actividades de salud pública, sobre todo las involucradas en la vigilancia y el deterioro de los laboratorios encargados de identificar cuanto antes a los microorganismos emergentes, así como la circulación en África y Asia de nuevas cepas de Vibrio cholerae O1 El Tor, las que producen la toxina del cólera clásico y reemplazan a la original del biotipo El Tor, ocasionando manifestaciones clínicas más graves, situación que representa un obstáculo importante para el control de esta enfermedad. En la lucha contra ésta en casos de desastre, la Organización Mundial de la Salud no recomienda el uso de las vacunas actuales, porque ocurre una rápida disminución en la protección, lo que da un sentido falso de la seguridad, debiéndose dirigir los recursos a los métodos de control más útiles. Dada la repercusión global que implica la reemergencia del cólera, en este trabajo se exponen algunos aspectos epidemiológicos, así como consideraciones en torno a las medidas de prevención y el control de esta entidad clínica, a partir de la revisión de diferentes fuentes de información actualizadas y la exposición de nuevos conceptos sobre su control, observaciones que serán de utilidad e interés para profesionales de todos los niveles de la atención sanitaria(AU)
Cholera is a health problem for many countries in the world. The high morbidity and mortality rates observed recently have concerned the scientific community, since the increase of the incidence of this disease could generate a global crisis in its control. Key factors in the reemergence of Cholera are: the general weakening of public health activities, especially those involved in the monitoring and deterioration of the laboratories responsible for early identification of emerging microorganisms as well as the circulation of new strains of Vibrio cholerae O1 El Tor in Africa and Asia, which produces the classical cholera toxin and replaces the original one of El Tor biotype, causing more severe clinical manifestations, which represents a major obstacle to control this disease. In the fight against this disease during the occurrence of disasters, the World Health Organization (WHO) does not recommend the use of existing vaccines against cholera because a rapid decline of protection occurs; giving a false sense of safety so resources must be directed to the most useful control methods. Due to the global impact the re-emergence of cholera involves, some epidemiological aspects and considerations on prevention and control of this clinical entity are presented in this article, starting by the review of different updated information sources and the presentation of new concepts on its control, which will be useful and interesting for health care professionals(AU)
Asunto(s)
Humanos , Cólera/epidemiología , Cólera/inmunología , Cólera/prevención & controlRESUMEN
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.
Asunto(s)
Vacunas contra el Cólera/administración & dosificación , Cólera/prevención & control , Administración Oral , Adolescente , Adulto , Anticuerpos Antibacterianos/sangre , Cólera/inmunología , Vacunas contra el Cólera/efectos adversos , Vacunas contra el Cólera/inmunología , Cuba , Método Doble Ciego , Femenino , Humanos , Masculino , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/efectos adversos , Vacunas Atenuadas/inmunología , Adulto JovenRESUMEN
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)
Asunto(s)
Humanos , Animales , Salud Bucal , Recién Nacido de Bajo Peso , Lactancia Materna , Ensayos Clínicos como Asunto/métodos , Ensayos Clínicos como Asunto/efectos adversos , CausalidadRESUMEN
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)
Asunto(s)
Humanos , Adolescente , Toxoide Diftérico/inmunología , Toxoide Tetánico/inmunología , Vacuna contra Difteria y Tétanos/inmunologíaAsunto(s)
Vacunas Meningococicas/uso terapéutico , Neisseria meningitidis Serogrupo B/inmunología , Envejecimiento , Preescolar , Cuba/epidemiología , Humanos , Lactante , Lipopolisacáridos/inmunología , Vacunación Masiva , Infecciones Meningocócicas/inmunología , Infecciones Meningocócicas/prevención & control , Vacunas Meningococicas/inmunología , Linfocitos T Colaboradores-Inductores/inmunologíaRESUMEN
Vibrio cholerae 638 is a living candidate cholera vaccine strain attenuated by deletion of the CTXPhi prophage from C7258 (O1, El Tor Ogawa) and by insertion of the Clostridium thermocellum endoglucanase A gene into the hemagglutinin/protease coding sequence. This vaccine candidate was previously found to be well tolerated and immunogenic in volunteers. This article reports a randomized, double-blind, placebo-controlled trial conducted to test short-term protection conferred by 638 against subsequent V. cholerae infection and disease in volunteers in Cuba. A total of 45 subjects were enrolled and assigned to receive vaccine or placebo. The vaccine contained 10(9) CFU of freshly harvested 638 buffered with 1.3% NaHCO(3), while the placebo was buffer alone. After vaccine but not after placebo intake, 96% of volunteers had at least a fourfold increase in vibriocidal antibody titers, and 50% showed a doubling of at least the lipopolysaccharide-specific immunoglobulin A titers in serum. At 1 month after vaccination, five volunteers from the vaccine group and five from the placebo group underwent an exploratory challenge study with 10(9) CFU of DeltaCTXPhi attenuated mutant strain V. cholerae 81. Only two volunteers from the vaccine group shed strain 81 in their feces, but none of them experienced diarrhea; in the placebo group, all volunteers excreted the challenge strain, and three had reactogenic diarrhea. An additional 12 vaccinees and 9 placebo recipients underwent challenge with 7 x 10(5) CFU of virulent strain V. cholerae 3008 freshly harvested from a brain heart infusion agar plate and buffered with 1.3% NaHCO(3). Three volunteers (25%) from the vaccine group and all from the placebo group shed the challenge agent in their feces. None of the 12 vaccinees but 7 volunteers from the placebo group had diarrhea, and 2 of the latter exhibited severe cholera (>5,000 g of diarrheal stool). These results indicate that at 1 month after ingestion of a single oral dose (10(9) CFU) of strain 638, volunteers remained protected against cholera infection and disease provoked by the wild-type challenge agent V. cholerae 3008. We recommend that additional vaccine lots of 638 be prepared under good manufacturing practices for further evaluation.
Asunto(s)
Vacunas contra el Cólera/administración & dosificación , Vacunas contra el Cólera/inmunología , Cólera/prevención & control , Vibrio cholerae/inmunología , Administración Oral , Adolescente , Adulto , Anticuerpos Antibacterianos/sangre , Bacteriófagos/genética , Celulasa/genética , Vacunas contra el Cólera/genética , Clostridium thermocellum , Método Doble Ciego , Heces/microbiología , Eliminación de Gen , Hemaglutininas/genética , Humanos , Masculino , Péptido Hidrolasas/genética , Vacunación , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/genética , Vacunas Atenuadas/inmunología , Vibrio cholerae/genética , Vibrio cholerae/patogenicidad , Vibrio cholerae/virologíaRESUMEN
OBJECTIVES: To evaluate the efficacy of vax-SPIRAL, a Cuban vaccine against leptospirosis, and to provide additional information concerning the safety of this vaccine (which was developed by Cuba's Finlay Institute). METHODS: This phase III efficacy trial of vax-SPIRAL was controlled, randomized, and double blind. The control vaccine used for the trial was Heberbiovac-HB (Heber Biotec, Cuba), a recombinant hepatitis B vaccine. The randomization unit for allocating persons to the study group or the control group were 523 family physician offices in the selected municipalities. The study covered the entire population of males and females from 20 to 64 years old who voluntarily agreed to participate, from the municipalities of Ranchuelo, Quemado, Santo Domingo, Encrucijada, Corralillo, Cifuentes, and Camajuaní, which are in the province of Villa Clara, in the central region of Cuba. The vaccinations were given in the physicians' offices between February and July 1998, with an interval of 6 weeks between the two doses. The follow-up period was 12 months. A case was considered positive if a person who had received the two doses of the vaccine became ill with leptospirosis more than 21 days after receiving the second dose, with the diagnosis confirmed through serological and microbiological methods. We calculated the efficacy of the vaccine and the relative risk of becoming ill with leptospirosis after the vaccination. For the safety study, two persons were chosen at random from among the individuals vaccinated at the office of each physician participating in the study. Follow-up of local and systemic adverse reactions was carried out by the family physicians during the seven days after the application of each dose. The level of statistical significance was set at 0.05. RESULTS: A total of 101 832 persons were vaccinated, with 50 354 of them (49.4%) receiving the leptospirosis vaccine and 51 478 of them (50.6%) receiving the control vaccine. The efficacy of the vax-SPIRAL vaccine was 78.1% (95% confidence interval (CI): 59.2% to 88.3%), and the relative risk of becoming ill with leptospirosis after receiving the leptospirosis vaccine was 0.22 (95% CI: 0.12 to 0.41). General discomfort was the most frequent systemic adverse reaction, and mild spontaneous pain at the injection site was the most frequent local effect. The local and systemic adverse reactions were both more frequent in the study group than in the control group (P = 0.003). There were no serious adverse events. CONCLUSION: The vax-SPIRAL vaccine proved to be safe and efficacious for leptospirosis control. The vaccine is recommended for use in preventing this disease among groups at risk of contracting it.
Asunto(s)
Vacunas Bacterianas , Leptospira/inmunología , Leptospirosis/prevención & control , Adulto , Vacunas Bacterianas/efectos adversos , Cuba , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJETIVOS: Evaluar la eficacia de la vacuna cubana contra la leptospirosis vax-SPIRAL y aportar información adicional acerca de la seguridad de esta vacuna. MÉTODOS: Ensayo de eficacia (fase III) controlado, aleatorizado y con doble enmascaramiento de la vacuna cubana contra la leptospirosis vax-SPIRAL (Instituto Finlay, Cuba). Como control se utilizó la vacuna recombinante contra la hepatitis B Heberbiovac-HB (Heber Biotec, Cuba). Como unidad de aleatorización para la asignación al grupo de estudio o al grupo testigo se emplearon los 523 consultorios de los médicos de familia existentes en los municipios seleccionados. El estudio abarcó a toda persona de 20 a 64 años de edad de uno u otro sexo que residía en los municipios de Ranchuelo, Quemado, Santo Domingo, Encrucijada, Corralillo, Cifuentes y Camajuaní, en la provincia de Villa Clara, ubicada en la región central de Cuba, que aceptó participar voluntariamente en el ensayo. La vacunación se efectuó en los consultorios de los médicos de familia entre febrero y julio de 1998, con un intervalo de 6 semanas entre las dos dosis. El período de seguimiento fue de 12 meses. Se consideró positivo un caso si había recibido las dos dosis de la vacuna asignada y había enfermado de leptospirosis, con diagnóstico confirmado mediante métodos serológicos y microbiológicos, después de 21 días de aplicada la segunda dosis. Se calcularon la eficacia de la vacuna y el riesgo relativo (RR) de enfermar de leptospirosis después de la vacunación. Para el estudio de seguridad se escogió a dos personas al azar entre las personas vacunadas en cada uno de los consultorios que participaron en el estudio de eficacia. El seguimiento de las reacciones adversas locales y sistémicas lo realizaron los médicos de familia durante los siete días posteriores a la aplicación de cada dosis. El nivel de significación se fijó en 0,05...
Objectives. To evaluate the efficacy of vax-SPIRAL, a Cuban vaccine against leptospirosis, and to provide additional information concerning the safety of this vaccine (which was developed by Cuba's Finlay Institute). Methods. This phase III efficacy trial of vax-SPIRAL was controlled, randomized, and double blind. The control vaccine used for the trial was Heberbiovac-HB (Heber Biotec, Cuba), a recombinant hepatitis B vaccine. The randomization unit for allocating persons to the study group or the control group were 523 family physician offices in the selected municipalities. The study covered the entire population of males and participate, from the municipalities of Ranchuelo, Quemado, Santo Domingo, Encrucijada, Corralillo, Cifuentes, and Camajuaní, which are in the province of Villa Clara, in the central region of Cuba. The vaccinations were given in the physicians' offices between February and July 1998, with an interval of 6 weeks between the two doses. The follow-up period was 12 months. A case was considered positive if a person who had received the two doses of the vaccine became ill with leptospirosis more than 21 days after receiving the second dose, with the diagnosis confirmed through serological and microbiological methods. We calculated the efficacy of the vaccine and the relative risk of becoming ill with leptospirosis after the vaccination. For the safety study, two persons were chosen at random from among the individuals vaccinated at the office of each physician participating in the study. Follow-up of local and systemic adverse reactions was carried out by the family physicians during the seven days after the application of each dose. The level of statistical significance was set at 0.05. Results. A total of 101 832 persons were vaccinated, with 50 354 of them (49.4%) receiving the leptospirosis vaccine and 51 478 of them (50.6%) receiving the control vaccine. The efficacy of the vax-SPIRAL vaccine was 78.1% (95% confidence interval (CI): 59.2% to 88.3%), and the relative risk of becoming ill with leptospirosis after receiving the leptospirosis vaccine was 0.22 (95% CI: 0.12 to 0.41). General discomfort was the frequent systemic adverse reaction, and mild spontaneous pain at the injection site was the most frequent local effect. The local and systemic adverse reactions were both more frequent in the study group than in the control group (P = 0.003). There were no serious adverse events. Conclusion. The vax-SPIRAL vaccine proved to be safe and efficacious for leptospirosis control. The vaccine is recommended for use in preventing this disease among groups at risk of contracting it.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Vacunas Bacterianas , Leptospira/inmunología , Leptospirosis/prevención & control , Vacunas Bacterianas/efectos adversos , Cuba , Método Doble CiegoRESUMEN
Estudia la relación entre la vegetación forestal y el medio ambiente. Se ocupa del caso puntual del río Reyes ubicado en la provincia de Jujuy de cuyas características naturales al ser alteradas han provocado problemas de torrenciales que inciden en la vida útil de la infraestructura de bienes y servicios y que repercuten socialmente. Estudia los bosques como componentes de un plan regulador, con un rol de importancia, si se los analiza considerando los beneficios directos que proporcionan a los valores hidráulicos, edáficos y ambientales
Asunto(s)
Argentina , Lluvia , Control de Crecidas , NieveRESUMEN
Estudia la relación entre la vegetación forestal y el medio ambiente. Se ocupa del caso puntual del río Reyes ubicado en la provincia de Jujuy de cuyas características naturales al ser alteradas han provocado problemas de torrenciales que inciden en la vida útil de la infraestructura de bienes y servicios y que repercuten socialmente. Estudia los bosques como componentes de un plan regulador, con un rol de importancia, si se los analiza considerando los beneficios directos que proporcionan a los valores hidráulicos, edáficos y ambientales