Wnt-responsive Lgr5-expressing stem cells are hair cell progenitors in the cochlea.

Auditory hair cells are surrounded on their basolateral aspects by supporting cells, and these two cell types together constitute the sensory epithelium of the organ of Corti, which is the hearing apparatus of the ear. We show here that Lgr5, a marker for adult stem cells, was expressed in a subset of supporting cells in the newborn and adult murine cochlea. Lgr5-expressing supporting cells, sorted by flow cytometry and cultured in a single-cell suspension, compared with unsorted cells, displayed an enhanced capacity for self-renewing neurosphere formation in response to Wnt and were converted to hair cells at a higher (>10-fold) rate. The greater differentiation of hair cells in the neurosphere assay showed that Lgr5-positive cells had the capacity to act as cochlear progenitor cells, and lineage tracing confirmed that Lgr5-expressing cells accounted for the cells that formed neurospheres and differentiated to hair cells. The responsiveness to Wnt of cells with a capacity for division and sensory cell formation suggests a potential route to new hair cell generation in the adult cochlea.

High depth, whole-genome sequencing of cholera isolates from Haiti and the Dominican Republic.

BACKGROUND: Whole-genome sequencing is an important tool for understanding microbial evolution and identifying the emergence of functionally important variants over the course of epidemics. In October 2010, a severe cholera epidemic began in Haiti, with additional cases identified in the neighboring Dominican Republic. We used whole-genome approaches to sequence four Vibrio cholerae isolates from Haiti and the Dominican Republic and three additional V. cholerae isolates to a high depth of coverage (>2000x); four of the seven isolates were previously sequenced. RESULTS: Using these sequence data, we examined the effect of depth of coverage and sequencing platform on genome assembly and identification of sequence variants. We found that 50x coverage is sufficient to construct a whole-genome assembly and to accurately call most variants from 100 base pair paired-end sequencing reads. Phylogenetic analysis between the newly sequenced and thirty-three previously sequenced V. cholerae isolates indicates that the Haitian and Dominican Republic isolates are closest to strains from South Asia. The Haitian and Dominican Republic isolates form a tight cluster, with only four variants unique to individual isolates. These variants are located in the CTX region, the SXT region, and the core genome. Of the 126 mutations identified that separate the Haiti-Dominican Republic cluster from the V. cholerae reference strain (N16961), 73 are non-synonymous changes, and a number of these changes cluster in specific genes and pathways. CONCLUSIONS: Sequence variant analyses of V. cholerae isolates, including multiple isolates from the Haitian outbreak, identify coverage-specific and technology-specific effects on variant detection, and provide insight into genomic change and functional evolution during an epidemic.

Cólera: historia de un gran flagelo de la humanidad / Cholera: history of a great calamity of the humanity

Se realizó una revisión bibliográfica con el objetivo de profundizar los conocimientos sobre el cólera y su historia. Se tratan aspectos relacionados con la etiología de la enfermedad, patogenia, cuadro clínico, tratamiento, epidemiología y prevención. El cólera es una enfermedad de origen multicausal donde intervienen factores biológicos, ambientales, sociales, políticos y culturales, la cual está resurgiendo como un problema sanitario de primera magnitud en muchos países. Para su erradicación es necesario desarrollar una fuerte promoción de salud en el seno de la sociedad, garantizar atención rápida a enfermos y contactos e impedir la desorganización de la estructura social y económica en pro de la calidad de vida del ser humano(AU)

A bibliographical revision with the objective of deepening in the knowledge on cholera and its history was carried out. Some aspects related with its aetiology, pathology, clinical picture, treatment, epidemiology and prevention are considered. Cholera is an illness of multicausal origin where biological, environmental, social, political and cultural factors intervene. This disease is resurging as a sanitary problem of first magnitude in many countries. It is necessary to develop a strong promotion of health in the society to eradicate it, to guarantee a quick attention to sick and contacts and to impede the disorganization of the social and economic structure in favour of the quality of the human being life(AU)

Comparison of the vibriocidal antibody response in cholera due to Vibrio cholerae O139 Bengal with the response in cholera due to Vibrio cholerae O1.

Vibrio cholerae serogroup O139, now considered to be the second organism capable of causing epidemic severe dehydrating cholera, contains a capsular polysaccharide which makes it difficult for it to be used in the conventional vibriocidal antibody assay optimized for V. cholerae O1. After modification of the procedure, which involved the use of specific bacterial strains, a lower bacterial inoculum, and increased amounts of complement, the vibriocidal antibody responses to V. cholerae O139 were measured in acute- and convalescent-phase sera from 33 V. cholerae O139-infected and 18 V. cholerae O1-infected patients and in single serum samples from 20 healthy control subjects. The responses in these individuals to V. cholerae O1 strains were also determined. Significant elevations in the homologous antibody response were found only in the convalescent-phase sera from both groups of patients with cholera. These findings may explain the basis for the lack of heterologous protection between the two serogroups of V. cholerae. Healthy controls had higher background levels of vibriocidal antibody to V. cholerae O1 than to V. cholerae O139.

Azithromycin in the treatment of cholera in children.

AIM: To evaluate the efficacy of azithromycin in the treatment of cholera in children. METHODS: A double-blind, randomized, controlled clinical trial on 80 children with acute watery diarrhoea and moderate to severe dehydration compared the efficacy of azithromycin and erythromycin in treating cholera. Data were analysed for 56 patients who were stool culture positive for Vibrio cholerae. In conjunction with rehydration therapy, 29 patients received azithromycin and 27 patients received erythromycin. Patients in the two treatment groups had comparable clinical and blood biochemical characteristics on admission. RESULTS: Patients who received azithromycin had significantly less stool output, shorter duration of diarrhoea and lower fluid intake compared with patients who received erythromycin. CONCLUSION: Azithromycin appears to be superior to erythromycin for treating cholera in children.

A novel kit for rapid detection of Vibrio cholerae O1.

We report on the development and testing of a novel, rapid, colorimetric immunodiagnostic kit, Cholera SMART, for direct detection of the presence of Vibrio cholerae O1 in clinical specimens. Unlike conventional culture methods requiring several days to complete, the Cholera SMART kit can be used directly in the field by untrained or minimally skilled personnel to detect V. cholerae O1 in less than 15 min, without cumbersome laboratory equipment. A total of 120 clinical and environmental bacterial strains, including both O1 and non-O1 serotypes of V. cholerae isolated from samples collected from a variety of geographical regions, were tested, and positive reactions were observed only with V. cholerae O1. Also, results of a field trial in Bangladesh, employing Cholera SMART, showed 100% specificity and 96% sensitivity compared with conventional culture methods. Another field trial, in Mexico, showed that Cholera SMART was 100% in agreement with a recently described coagglutination test when 108 stool specimens were tested.

Field trial of oral cholera vaccines in Bangladesh: results from three-year follow-up.

The protective efficacy (PE) of B subunit killed whole-cell (BS-WC) and killed whole-cell-only (WC) oral cholera vaccines was assessed in a randomised double-blind field trial among children aged 2-15 years and women over 15 years in rural Bangladesh. Among the 62 285 subjects who received three doses of BS-WC, WC, or Escherichia coli K12 strain placebo, cumulative PE at 3 years of follow-up was 50% for BS-WC and 52% for WC. PE was similar against severe and non-severe cholera, but was significantly lower in children who were vaccinated at 2-5 years (26% for BS-WC; 23% for WC) than in older persons (63% for BS-WC; 68% for WC). Among persons vaccinated at 2-5 years, protection at 4-6 months of follow-up was similar to that for older persons, but rapidly waned thereafter and was not evident during the third year of follow-up. In contrast, persons vaccinated at older ages were protected even in the third year of follow-up (PE 40% for BS-WC; 62% for WC). PE was substantially higher against classical cholera (58% for BS-WC; 60% for WC) than against El Tor cholera (39% and 40%).

Cólera: mitos e realidade / Cholera: miths and reality

A cólera é doença diarreica aguda do intestino delgado causada pelo Vibrio cholerae 01, microrganismo que possui forte potencial epidemico. Desde 1817 houve seis pandemias da doença e atualmente estamos vivenciando a sétima. É doença veiculada pela água de transmissäo fecal-oral, relacionando-se diretamente com as precarias condiçöes sanitárias experimentadas pela populaçäo atingida.Por ser doença secular, de importância mundial e potencial fatal, a cólera é cercada por mitos que foram recentemente revividos pelas autoridades de saúde e populaçäo durante a chegada da sétima pandemia ao Brasil, no final de 1991. E com o objetivo de esclarecer alguns desses aspectos, que claramente prejudicam o manuseio e controle da doença, que elaboramos o presente artigo

Cólera: revisäo / Cholera: a review

É apresentada uma revisäo no que diz respeito aos aspectos etiológico, epidemiológico, fisiopatológico, clínico e terapêutico da cólera

Manual para la vigilancia epidemiológica del cólera en México / Handbook for the epidemiologic surveillance of cholera in Mexico

El cólera es un padecimiento infeccioso agudo, producido por el VIBRIO CHOLERAE, caracterizado por la aparición brusca de diarrea abundante que puede llevar a la deshidratación, choque hipovolémico y muerte en pocas horas. A efecto de prevenir, controlar y atender los brotes de cólera, las autoridades mexicanas de salud difunden por medio de diversos medios, pero particularmente a través de esta publicación, información integral y actualizada sobre los aspectos clínicos, epidemiológicos y de diagnóstico más relevantes sobre dicho padecimiento. Este manual incluye información general acerca del padecimiento: antecedentes, epidemiología, agente infeccioso, procedimientos para la vigilancia epidemiológica, cuadro clínico, diagnóstico y tratamiento, acciones ha desarrollar para el estudio de brotes y medidas de prevención

Manejo hospitalario del paciente con colera. Brote en la parroquia de Cangahua. Cantón Cayambe, 1995. Hospital Raúl Maldonado Mejía

En mayo de 1995, el Hospital Raúl Maldonado Mejía de Cayambe recibió a 43 pacientes del brote colérico de la parroquía de Cangahua (cayambe), el cual resultó por la compartición de comidas y bebidas durante el velorio de la primera infectada fallecida. El 35 por ciento llegaron con deshidratación grado 3 y 16 por ciento en shock. La media del tiempo de hospitalización fue 3.63 días de los 43 casos ninguno falleció ni presentaron complicación alguna...

Vacunas contra el cólera / Vaccines against cholera

El cólera es una enfermedad aguda e infecciosa que fue descrita antes de la época de Hipócrates en el siglo V AC. Se describieron varias epidemias de esta enfermedad en Asia entre los siglos XV y XVIII. A mediados del siglo XIX John Snow en Inglaterra fue el primero en describir las medidas de prevención de la enfermedad a raíz de una epidemia ocurrida en Londres. En 1883, Robert Koch realizó el descubrimiento del agente causal, Vibrio cholerae, un bacilo curvo de gran movilidad. Durante los siglos XIX y XX han ocurrido siete pandemias de cólera; en la actualidad ocurre la transmisión de la séptima. El cólera es una de las causas más importantes de morbilidad y mortalidad de algunos países de Asia y Africa y desde 1991 también en Latinoamérica. Desde principios del siglo se ha empleado una vacuna parenteral elaborada con una cepa de V. cholerae 01, inactivada con calor, la cual únicamente induce 50 por ciento de protección en jóvenes y adultos, durante un período de aproximadamente 6 meses. El empleo de adyuvantes no ha tenido influencia en su eficiencia, sino por el contrario incrementa las reacciones colaterales. Las perspectivas para el desarrollo de una vacuna eficaz contra el cólera se basan en el hecho de que más del 90 por ciento de los sujetos infectados en forma natural quedan protegidos para una segunda reinfección. El avance del desarrollo de las vacunas del cólera se ha podido efectuar gracias a un mejor conocimiento de los mecanismos de patogenicidad y antigenicidad del agente etiológico, aunque persisten incógnitas importantes. La vacuna ideal contra el cólera debería ser tan eficaz como la infección natural, sin riesgo de causar enfermedad infecciosa, de fácil administración, de bajo costo, de una sola dosis, inocua, que proteja contra la infección y obviamente contra la enfermedad grave, con protección de larga duración y probablemente de administración oral