Expression in Saccharomyces boulardii of recombinant Toxin-coregulated pilus A subunit (TcpA) of Vibrio cholerae O1

Cholera is endemic in over 50 countries with an estimated mortality of 100,000-120,000. Vaccination is considered the complementary key to prevent and control cholera; therefore, alternative vaccine preparations are needed. Toxin Co-regulated Pilus is part of the toxR virulence regulon, which is necessary for colonization in the intestinal mucosa. In order to express Vibrio cholerae TcpA protein in Saccharomyces boulardii, the expression plasmid pYES2 was constructed by inserting tcpA gene isolated from local Vibrio cholerae Eltor Inaba isolates. The new construct was transferred into Saccharomyces boulardii cells and the expression of tcpA gene was induced from the GAL1 promoter by adding galactose to the medium. The SDS-PAGE and Western blot analysis showed the presence of TcpA in yeast. These results showed that Saccharomyces boulardii is a promising host to express Vibrio cholerae toxin TcpA as the first step in attempt to produce an oral Vibrio cholerae vaccine(AU)

El cólera es endémico en más de 50 países. Se estima una mortalidad entre 100.000 - 120.000 debido a esta enfermedad. La vacunación se considera una medida complementaria para prevenir y controlar el cólera, por lo tanto, se necesitan preparaciones vacunales alternativas a las existentes. El Pili corregulado con la toxina, es parte del regulón de virulencia toxR, y es necesario para la colonización en la mucosa intestinal. Para expresar la proteína tcpA de Vibrio cholerae en Saccharomyces boulardii, se construyó el plásmido de expresión pYES2 insertando el gen tcpA obtenido a partir de aislamientos locales de Vibrio cholerae El Tor Inaba. La nueva construcción se transfirió a las células de Saccharomyces boulardii y se indujo la expresión del gen tcpA a partir del promotor GAL1 mediante la adición de galactosa al medio. El análisis mediante SDS-PAGE y Western blot demostró la presencia de TcpA en levaduras. Los resultados demostraron que Saccharomyces boulardii es un hospedero prometedor para expresar el gen tcpA de Vibrio cholerae como el primer paso en el intento de producir una vacuna oral contra Vibrio cholerae(AU)

Ensayo de inmunogenicidad y toxicidad aguda del candidato vacunal contra el cólera vax-COLER® / Immunogenicity and acute toxicity assay of the vaccine candidate against cholera vax-COLER®

Para el control y prevención del cólera humano se han llevado a cabo diferentes estrategias, entre las cuales, la vacunación es una de las medidas más eficaces. La evaluación preclínica de candidatos vacunales requiere de la demostración de la seguridad de los mismos, para lo cual los estudios toxicológicos son determinantes, al ser obligatorios y altamente regulados. Este estudio tuvo como objetivo demostrar la relevancia de las ratas Sprague Dawley como biomodelo a través de su respuesta inmunológica al candidato vacunal contra el cólera, vax-COLER®, utilizando la técnica de determinación de anticuerpos vibriocidas. Además, evaluar los efectos toxicológicos locales y sistémicos por la administración de una dosis de vax-COLER® a través de la evaluación de síntomas, del consumo de agua y alimentos, el peso corporal y estudios anatomopatológicos. La vacuna vax-COLER® resultó inmunogénica y no evidenció síntomas ni muertes, no hubo cambios en el peso corporal y los consumos de agua y alimentos se comportaron de forma similar entre todos los grupos. Los estudios anatomopatológicos solo mostraron cambios a nivel histológico en los ganglios linfáticos mesentéricos y placas de Peyer de los animales vacunados, con presencia de hiperplasia de los folículos secundarios subcapsulares, hallazgo que difirió significativamente con el resto de los grupos. Se concluye que la vacuna vax-COLER® es inmunogénica en ratas Sprague Dawley, demostrando la relevancia del biomodelo para la evaluación de la seguridad preclínica y que la aplicación de una dosis no produjo efectos tóxicos agudos generales ni locales(AU)

Different strategies have been carried out for the control and prevention of human cholera. Vaccination is one of the most effective strategies. Preclinical evaluation of vaccines needs to prove their safety; whereby toxicological studies are decisive. They are mandatory and highly regulated. This study was aimed to demonstrate the relevance of Sprague Dawley rats as a biomodel, through the immunological response to vax-COLER® cholera vaccine, using the technique of determination of vibriocidal antibodies. In addition, local and systemic toxicological effects were evaluated after administration of a dose of vax-COLER®; through the evaluation of symptoms, water and food consumption, body weight and anatomopathological studies. The vax-COLER® vaccine was immunogenic and showed no symptoms or deaths. No changes in body weight were detected, and food and water consumption were similar among all groups. The anatomopathological studies showed histological changes in the mesenteric lymph nodes and Peyer's patches of the vaccinated animals, with hyperplasia of the subcapsular secondary follicles, finding that differed significantly from the rest of the groups. It is concluded that vax-COLER® vaccine is immunogenic in Sprague-Dawley rats, demonstrating the relevance of the biomodel for the evaluation of preclinical safety, as well as that the application of a single dose did not produce acute general or local toxic effects(AU)

Representaciones, discursos y prácticas profilácticas durante la epidemia de cólera (1886-1887, Mendoza, Argentina) / Prophylactic representations, discourses and practices during the cholera epidemic (1886-1887, Mendoza, Argentina)

Resumen El artículo busca indagar en los proyectos de disciplinamiento sancionados por el Estado de la provincia de Mendoza (Argentina) durante la epidemia de cólera ocurrida en el verano de 1886 y 1887. Si bien los planes tenían como finalidad mejorar el estado sanitario de toda la población y de la ciudad, apuntaron y se aplicaron con mayor intensidad sobre los sectores populares y sus espacios. Esto se debió a las ideas y representaciones que en torno de la enfermedad y la muerte construyó el grupo dirigente durante estos periodos.

Abstract The article takes a look into the disciplinary projects approved by the authorities in the province of Mendoza (Argentina) during the cholera epidemic that took place during the summer of 1886-1887. Although the projects were intended to ameliorate the sanitary conditions of the whole of the population, these were focused and applied more intensively on the underprivileged sectors and their areas of inhabitance. This follows the ideas and representations created by the State regarding the illness and its death during this period.

Protocolo del Sistema Nacional de Vigilancia Epidemiológica: enfermedades transmitidas por agua y alimentos. No. 03 / Protocol of the National Epidemiological Surveillance System: water and foodborne diseases. No. 03

Estos protocolos están dirigido a personal médico, paramédico y otros profesionales que realizan acciones gerenciales y operativas de vigilancia epidemiológica en los servicios de salud del país, y están divididos en varios tomos para dar a conocer y actualizar la identificación y medidas de control para diversos padecimientos a fin de continuar con el mejoramiento de las capacidades técnicas de los trabajadores de salud, que permita planificar la prestación de servicios con decisiones partiendo de un enfoque epidemiológico comprobado, para responder a los cambios de tendencias epidemiológicas y con ello contribuir al fortalecimiento de prácticas asertivas de la salud pública de nuestro país. Las enfermedades transmitidas por alimentos y agua (ETA´s), constituyen un importante problema de Salud Pública, debido a su magnitud, trascendencia, tendencia fluctuante y aumentos en su comportamiento durante el año, lo que ha significado etapas de emergencia, re emergencia, aparición de agentes nuevos con potencial epidémico y el incremento a la resistencia a los antimicrobianos con impacto negativo económico, en grupos de población. Las enfermedades transmitidas por alimentos y agua, se registran entre las primeras diez causas de morbilidad y mortalidad en el país; evento notificado como enfermedad diarreica, con frecuencia los servicios de salud tienen poca capacidad de respuesta para identificación del agente etiológico, limitándose a implementar medidas de control eficientes de las fuentes de infección o contaminación y divulgación de acciones dirigidas a minimizan los factores de riesgo identificados.

Yemen OCV risk assessment

The Ministry of Public Health and Population [MoHP], Yemen, WHO and other partners conducted assessment to determine risk profile of governorates and districts for occurrence and spread of cholera in order to prioritize the high risk districts for use of oral cholera vaccine [OCV] as a preventive measure for prevention and control of cholera

OCV risk assessment in Sudan

In October 2017, the Federal Ministry of Health, Sudan, in collaboration with WHO and other partners conducted as-sessment to determine risk profile of states and localities for occurrence and spread of cholera in order to prioritize localities and special high risk groups for use of oral cholera vaccine [OCV] for prevention of the outbreak

Control de foco de un brote de Cólera. Matanzas 2014 / Control of Focus in front of a Bud of Cholera. Matanzas 2014

Se presenta un estudio de control de foco de un brote de cólera, mediante la técnica observacional del tipo serie de casos, en el mes de julio de 2014 en el Municipio Matanzas, donde se describe, según el método epidemiológico, la relación de los casos detectados con el caso índice; se analiza el problema detectado teniendo en cuenta el enfoque de riesgo del cólera. Se realiza una evolución clínico-epidemiológica de los casos detectados y se analizan las medidas de control de foco aplicadas. Se revisan tanto las historias clínicas individuales en el consultorio del médico de la familia, como las encuestas epidemiológicas y el expediente de control de foco en el departamento de Epidemiología (AU).

A study of control of focus of a bud of cholera is presented, by means of the observational technique of the type series of cases, in the month of July of 2014 in the Municipality Matanzas, where it is described, according to the epidemic method, the relationship of the cases detected with the index case; the detected problem is analyzed keeping in mind the focus of risk of the cholera. He/she is carried out a clinical-epidemic evolution of the detected cases and of the applied measures of focus control. They are revised the clinical histories so much in the clinic of the doctor of the family, as the epidemic surveys and the file of focus control in the department of epidemiology (AU).

Oral cholera vaccination in hard-to-reach communities, Lake Chilwa, Malawi

Objective To evaluate vaccination coverage, identify reasons for non-vaccination and assess satisfaction with two innovative strategies for distributing second doses in an oral cholera vaccine campaign in 2016 in Lake Chilwa, Malawi, in response to a cholera outbreak. Methods We performed a two-stage cluster survey. The population interviewed was divided in three strata according to the second-dose vaccine distribution strategy: (i) a standard strategy in 1477 individuals (68 clusters of 5 households) on the lake shores; (ii) a simplifiedcold-chain strategy in 1153 individuals (59 clusters of 5 households) on islands in the lake; and (iii) an out-of-cold-chain strategy in 295 fishermen (46 clusters of 5 to 15 fishermen) in floating homes, called zimboweras. Finding Vaccination coverage with at least one dose was 79.5% (1153/1451) on the lake shores, 99.3% (1098/1106) on the islands and 84.7% (200/236) on zimboweras. Coverage with two doses was 53.0% (769/1451), 91.1% (1010/1106) and 78.8% (186/236), in the three strata, respectively. The most common reason for non-vaccination was absence from home during the campaign. Most interviewees liked the novel distribution strategies. Conclusion Vaccination coverage on the shores of Lake Chilwa was moderately high and the innovative distribution strategies tailored to people living on the lake provided adequate coverage, even among hard-to-reach communities. Community engagement and simplified delivery procedures were critical for success. Off-label, out-of-cold-chain administration of oral cholera vaccine should be considered as an effective strategy for achieving high coverage in hard-to-reach communities. Nevertheless, coverage and effectiveness must be monitored over the short and long term

Cholera outbreak in Somalia

The Ministry of Health of Somalia reported a total of 5,257 cumulative cases of suspected cholera including 84 deaths [CFR 1.6%] from January to December 2015 to WHO, The outbreak is still continuing in several districts in the Southern and Central Regions

Use of single dose OCV: New strate-gies for cholera control

Recent evidence has emerged on the effectiveness of single dose of oral cholera vaccine for outbreak response. This finding has generated interest in the control of cholera outbreaks in the epidemic belt of the Eastern Mediterranean Region

Prevalence of cholera risk factors between migrant Haitians and Dominicans in the Dominican Republic / Prevalencia de los factores de riesgo de cólera entre los inmigrantes haitianos y los dominicanos en la República Dominicana

OBJECTIVE: To determine whether cholera risk factor prevalence in the Dominican Republic can be explained by nationality, independent of other factors, given the vulnerability of many Haitians in the country and the need for targeted prevention. METHODS: A cross-sectional, observational household survey (103 Haitian and 260 Dominican) was completed in 18 communities in July 2012. The survey included modules for demographics, knowledge, socioeconomic status, and access to adequate water, sanitation, and hygiene (WASH) infrastructure. Logistic regression assessed differential access to WASH infrastructure and Poisson regression assessed differences in cholera knowledge, controlling for potential confounders. RESULTS: Dominican and Haitian households differed on demographic characteristics. Haitians had lower educational attainment, socioeconomic status, and less knowledge of cholera than Dominicans (adjusted odds ratio [aOR] = 0.66; 95% confidence interval [95%CI] = 0.55-0.81). Access to improved drinking water was low for both groups, but particularly low among rural Haitians (aOR = 0.21; 95%CI: 0.04-1.01). No differences were found in access to sanitation after adjusting for sociodemographic confounders (aOR = 1.00; 95%CI: 0.57-1.76). CONCLUSIONS: Urban/rural geography and socioeconomic status play a larger role in cholera risk factor prevalence than nationality, indicating that Haitians' perceived vulnerability to cholera is confounded by contextual factors. Understanding the social dynamics that lead to cholera risk can inform control strategies, leading to better targeting and the possibility of eliminating cholera from the island.

OBJETIVO: Determinar si la prevalencia de los factores de riesgo de cólera en la República Dominicana puede explicarse por la nacionalidad, independiente de otros factores, dada la vulnerabilidad de muchos habitantes haitianos que viven en el país y la necesidad de actividades de prevención orientadas. MÉTODOS: En julio del 2012, se llevó a cabo una encuesta domiciliaria transversal y de observación (103 hogares haitianos y 260 hogares dominicanos) en 18 comunidades. La encuesta incluía módulos sobre características demográficas, conocimientos, nivel socioeconómico y acceso a una infraestructura adecuada de agua, saneamiento e higiene (WASH). Mediante regresión logística, se evaluaron las diferencias de acceso a una infraestructura de WASH y, mediante regresión de Poisson, se evaluaron las diferencias en materia de conocimientos sobre el cólera, con control de los potenciales factores de confusión. RESULTADOS: Los hogares dominicanos y haitianos diferían en cuanto a características demográficas. Los segundos mostraban un nivel educativo inferior, una peor situación socioeconómica y menores conocimientos sobre el cólera que los hogares dominicanos (razón de posibilidades ajustada [ORa] = 0,66; intervalo de confianza de 95% [IC95%] = 0,55-0,81). El acceso a agua potable mejorada fue bajo en ambos grupos pero particularmente entre los hogares haitianos rurales (ORa = 0,21; IC95%: 0,04-1,01). No se observaron diferencias en cuanto al acceso al saneamiento después de ajustar para los factores de confusión sociodemográficos (ORa = 1,00; IC95%: 0,57-1,76). CONCLUSIONES: La geografía urbana o rural y el nivel socioeconómico repercuten más ampliamente en la prevalencia de los factores de riesgo de cólera que la nacionalidad, lo que indica que la vulnerabilidad percibida de los habitantes haitianos al cólera se confunde por factores contextuales. La comprensión de la dinámica social que conduce al riesgo de cólera puede servir de base a las estrategias de control, y llevar a una mejor orientación de las iniciativas y a la posibilidad de eliminar el cólera de la isla.

Cholera outbreak in Iraq

Between 15 September to 19 November 2015, the Ministry of Health of Iraq reported to WHO a total of 4,864 labor-atory-confirmed cases of cholera. How-ever, when re-tested at the Central Public Health Laboratory [CPHL] in Baghdad, a total of 2,847 stool samples were found positive for Vibrio cholera 01 Inaba

Evaluación de la vigilancia del cólera en el policlínico Héroes del Moncada / Evaluation of cholera surveillance at Heroes of Moncada polyclinic

Introducción: la evaluación está concebida como la actividad que permite emitir un juicio de valor. El cólera constituye una enfermedad infecciosa conocida desde tiempos inmemoriales, por lo que desde hace más de 40 años ha sido objeto de vigilancia en Cuba. Múltiples y complejas variables han sido las responsables de la entrada del Vibrio cholerae en el país, condicionando la aparición en el territorio nacional de diversos brotes. Objetivo: evaluar la vigilancia del cólera en el policlínico Héroes del Moncada del municipio Plaza de la Revolución, en el período de octubre-noviembre de 2012. Método: se realizó un estudio descriptivo, transversal, de evaluación táctica. El universo estuvo conformado por: 26 médicos de consultorios de médico de familia, un vicedirector de Higiene y Epidemiología, 3 técnicas de laboratorios, dos de estadísticas y 3 técnicos de Higiene del área. Se seleccionó una muestra por conveniencia que representó el 20 por ciento del universo. Se aplicó la metodología de la evaluación rápida propuesta por la Dra. Teresa Fariñas, visitándose en un período de 2 días un total de 5 consultorios del policlínico. Además se recogió información retrospectiva del mes de octubre y primera quincena de noviembre. Resultados: se identificaron brechas entre lo que estaba orientado vigilar por los médicos y enfermeras de la familia ante todo caso que solicitara atención médica por padecer de una enfermedad diarreica aguda y lo que en realidad se estaba realizando. Conclusiones: la valoración de la vigilancia del cólera en nuestro estudio fue evaluada de medianamente satisfactoria, al calificarse como no útil, con una calidad medianamente aceptable y unos resultados satisfactorios...

evaluation is conceived as the activity that allows a judgment of value. Cholera is an infectious disease known since ancient times, so for more than 40 years it has been under surveillance in Cuba. Multiple and complex variables have been responsible for the entry of Vibrio cholerae in Cuba, conditioning the emergence of several outbreaks on the national territory. Objective: to assess cholera surveillance at Heroes of Moncada polyclinic in Plaza Township, Havana from October to November 2012. Method: a tactical, descriptive, cross-sectional study assessment was performed. The universe consisted of 26 medical practices, a principal assistant of Hygiene and Epidemiology, 3 laboratory technicians, 2 of statistics technicians, and 3 hygiene technicians from this area. A convenience sample was selected representing 20 percent of the universe. The rapid assessment methodology proposed by Dr. Teresa Fariñas was applied, visiting 5 medical practices of this area over a total period of two days. Further background information from October and first half of November was collected. Results: gaps were identified between what was primarily instructed to control by family physicians and nurses in case of health care due to acute diarrheal disease and what actually was taking place. Conclusions: the evaluation of cholera surveillance in our study was assessed fairly satisfactory, by being scored as unuseful, with a fairly acceptable quality and satisfactory results...

Cholera outbreak in South Sudan requires vigilance in Sudan

The ministry of Health of South Sudan officially declared an outbreak of cholera in the capital, Juba on 15th May 2014. Since the start of the outbreak on 23 April 2014, up to 2 June 2014, a total of 1209 cases including 29 deaths [CFR 2.4%] have been reported. 99% of the cases have been reported from Juba County in Central Equatoria State. Nine out of 15 Payams [districts] in the County have reported cases of cholera. The outbreak is spreading northward and suspected cases have been reported from Kaka in Manyo County in the border with Sudan

Safety and Immunogenicity Assessment of an Oral Cholera Vaccine through Phase I Clinical Trial in Korea

The safety, tolerability and immunogenicity of an oral cholera vaccine (OCV) was assessed in adult Korean male through an open-label, non-comparative clinical study. Two doses of vaccine with an interval of 2 weeks were given to 20 healthy subjects. A total of 7 adverse events occurred in 6 subjects. However, no clinically significant change was observed in electrocardiograms, vital signs, physical examinations, and clinical laboratory tests. The immunogenicity of OCV was evaluated by serum vibriocidal assay where anti-Vibrio cholerae O1 and O139 antibodies were measured at day 0, 14, and 28 of vaccine administration. The antibody titers ranged from < 2.5-5,120 for V. cholerae O1 Inaba, < 2.5-10,240 for V. cholerae O1 Ogawa and < 2.5-480 for V. cholerae O139. In addition, the fold increase in antibody titers ranged from 1-4,096 for O1 Inaba, 1-8,192 for O1 Ogawa, and 1-384 for O139. The seroconversion rate was 95% and 45% for O1 and O139 antibodies, respectively. Our study clearly shows that administration of two doses of OCV at a 2 week-interval increases an appropriate level of antibody titer in the serum of healthy Korean adult males (Clinical Trial Number, NCT01707537).

La promoción y prevención de salud es la piedra angular para erradicar el cólera en el primer nivel de atención / Prevention and promotion is the cornerstone in the effort to erradicate cholera in primary care

Introducción:el Cholera morbus ha acompañado a la humanidad desde tiempos inmemoriales. Existen antecedentes en China, India y la Grecia clásica. Sin embargo, sólo se registran datos a partir de 1817 cuando se documenta la primera pandemia surgida en Asia y que se extendió a Turquía y los países árabes. Desde entonces se han sucedió ocho episodios pandémicos de cólera en el mundo. Objetivo: comunicar a la comunidad científica sobre la situación epidemiológica ocurrida en el mes de julio de 2012 en la provincia de Granma, de las medidas de promoción y prevención de salud que se desarrollaron en el primer nivel de atención para el cuadro diarreico causado por el Vibrio cholerae. Estas medidas las implementaron los equipos básicos de salud en el territorio con la participación intersectorial, lo que redunda en la adopción de estilos de vida saludables por parte de la población en general. Conclusión: primaron las actividades de saneamiento ambiental para disminuir la propagación de la enfermedad, complementadas con sugerencias a la comunidad médica sobre la importancia de la vigilancia epidemiológica ante eventuales reemergentes similares.

Introduction.Cholera has accompanied mankind since time immemorial with historical records from China, India and ancient Greece. However, registers are available only since 1817, when the first documented pandemic emerged in Asia and spread to Turkey and Arab countries. Since then, eight episodes of cholera pandemic have occurred in the world. Objective. To inform the scientific community about the epidemiological situation in the province of Granma, Cuba, at the cross-sectional period of July 2012 and the prevention and health promotion measures that were introduced in the first level of care for cases of diarrhea caused by Vibrio cholerae. These measures were implemented in the territory with an intersectoral approach, resulting in the adoption of healthy lifestyles by the general population. Conclusion. Basic sanitation activities were undertaken to slow the spread of the disease, complemented by suggestions to the medical community about the importance of epidemiological surveillance to detect reemergence.

Entre o Carlo R. e o Orleannais: a saude publica e a profilaxia maritima no relato de dois casos de navios de imigrantes no porto do Rio de Janeiro, 1893-1907 / Between the Carlo R. and the Orleannais: public health and maritime prophylaxis in the description of two cases of ships transporting immigrants arriving in the port of Rio de Janeiro, 1893-1907

Aborda as mudanças ocorridas nas práticas da profilaxia marítima brasileira. Por meio de dois casos de navios de imigrantes, que chegaram ao porto do Rio de Janeiro com epidemias a bordo, são analisados a compreensão sobre a etiologia, a forma de prevenção e o combate às três doenças com regulamentação portuária internacional: febre amarela, peste bubônica e cólera. Até o final do século XIX, uma das principais práticas de profilaxia era a quarentena. No início do XX, identificamos a emergência do ideário da microbiologia e dos vetores no serviço sanitário dos portos. A quarentena, que já vinha sendo criticada como antiquada e ineficaz, é limitada a alguns casos, e novos métodos e tecnologias da higiene passam a ser aplicados na defesa sanitária dos portos.

We address the changes in Brazilian maritime prophylaxis by studying two cases of immigrant ships arriving at the port of Rio de Janeiro with epidemics onboard. The objective is to understand the etiology, means of prevention and methods used to combat the three diseases subject to international port regulations: yellow fever, bubonic plague and cholera. Until the late nineteenth century, quarantines were one of the main disease prevention practices. In the early twentieth century, microbiology and the concept of vectors in ports sanitation services emerged. Quarantines, which were already being criticized as antiquated and ineffective, were limited to a few cases, and new hygiene methods and technologies began to be applied in port sanitary defense.