Virología de los rotavirus y epidemiología de la diarrea por rotavirus

Artículo científico -- Universidad de Costa Rica. Instituto de Investigaciones en Salud, 1985Rotaviruses are a leading cause of morbid- feeding infants and children of tender age ity and mortality from diarrhea among breast- everywhere in the world, and particularly in microorganisms replicate in the villose epithelium of the small intestine and cause diarrhea by denudation, atrophy of the villi and impairment of the absorptive capacity of the enterocytes. They constitute a separate genus in the family of the Reoviridae, and are believed to have evolved through cumulative "drift" and "shift" changes as well as exchange of segments of the RNA. They were discovered late because of their requirements of culture systems and media, which also made it difficult to develop them in experimental conditions. The use of trypsin to mediate the rupture of the outer capsid polypeptide facilitated the culture of human strains by prior passage through piglets and subsequently by continuous histoculture in monkey kidney. This procedure yielded sylvatic human strains. The human strains of rotavirus have been classified in four serotypes and two subgroups by such techniques as complement fixation, immune adherence hemagglutination, and enzymelinked immunosorbent assay (ELISA). Electrophoresis in polyacrylamide gel also permits the typing of strains prevalent in a community or particular environment over a given period of time, and affords immediate identification of the antigenic subgroup by the pattern of RNA segment migration. The immunoassay methods currently preferred for detection of the rotavirus antigen and antibody are ELISA and the solid-phase radio-immunoassay (RIA) procedures, which are sensitive and straightforward. The evaluation of neutralizing antibodies in certain serotypes has recently been simplified by the new neutralization procedure by plaque reduction. The principal propagators of the virus are children with diarrhea, who frequently transmit a mild or asymptomatic infection to their contacts. Although human susceptibility, unlike that of other mammals, is lower in the first six months of life, neonates with asymptomatic infection have been frequently seen in large hospitals, and in some countries severe diarrhea outbreaks have been reported. Hospital wards are ideal environments for the spread of the virus because of the low immunity of newborns and the high concentration, stability and resistance of the virus. In nonimmune populations this has been the cause of major epidemics in all age groups, and sporadic outbreaks have been reported among hospitalized adults L. and old people. However, there is little information on true rates of prevalence and incidence of rotavirus infections. Incidences peak in the colder months both in temperate and tropical climates. Infections are less frequent or less pathogenic in hygienic rural areas where breast-feeding is protracted. As a result of experiments in animals, the immunization of expectant mothers is currently under consideration to raise the antibody titer in their milk. The possibilities for vaccination are beginning to show promise, but several important problems remain. The optimal vaccinating age has to be determined and there has been as yet no success in discovering the right vaccine strain or a method for the production of human strain in quantities sufficient for mass vaccinations. In Finland studies have begun on the preparation of an oral vaccine based on a heterologous bovine rotavirus, which has given encouraging results. Recent molecular cloning of rotavirus genes is another possibility for the production of a suitable vaccine strain, which is a growing need particularly for developing countriesLos rotavirus son una de las causas principales de morbilidad y mortalidad por diarrea entre lactantes y niños de corta edad en todas partes del mundo, especialmente en los países menos desarrollados. Esos microorganismos se replican en el epitelio velloso del intestino delgado ocasionando diarrea por denudación, atrofia del vello y disminución de la capacidad de absorción de los enterocitos. Constituyen un género separado dentro de la familia de los Reoviridae y se cree que su evolución es consecuencia de cambios acumulativos provocados por desviación, transposición e intercambio de segmentos del ARN. Su descubrimiento fue tardío debido a sus exigencias en cuanto al medio y sistemas de cultivo, lo cual dificultó también su desarrollo en condiciones experimentales. La utilización de tripsina coma mediador de la ruptura del poli péptido exterior de la cápside facilito el cultivo de cepas humanas mediante pasajes preliminares en lechones y, subsecuentemente, histocultivos continuos en riñón de mono. Este método permitió cultivar cepas humanas de tipo silvestre. Las cepas humanas de rotavirus se han clasificado en cuatro serotipos y dos subgrupos con la ayuda de técnicas como la fijación del complemento, la hemaglutinación por inmunoadherencia y la inmunoabsorción enzimática (ELISA). La electroforesis en gel policrilamfídico además posibilita la tipificación de cepas prevalentes en una comunidad o medio especial durante un periodo determinado, permitiendo la identificación a primera vista del subgrupo antigénico por la pauta de migración de los segmentos de ARN. Entre los métodos de inmunoensayo para la detección del antígeno y anticuerpo del rotavirus, actualmente se prefieren el ELISA y el radioinmunoensayo de fase solida (RIA), que son sensibles y fáciles. Recientemente, el nuevo procedimiento de neutralización por reducción de placas ha simplificado la evaluación de los anticuerpos neutralizadores de determinados serotipos. Los principales propagadores del virus son los niños con diarrea, que frecuentemente transmiten una infección leve o asintomática a sus contactos. Aunque la susceptibilidad del hombre, a diferencia de los otros mamíferos, es menor en los primeros seis meses de vida, en grandes hospitales se han observado casos frecuentes de neonatos con infección asintomática, en tanto que en algunos países se han notificado brotes de diarrea grave. Las salas de hospital son ideales para la dispersión del virus, por la reducida inmunidad de los recién nacidos y la alta concentración, estabilidad y resistencia del virus. En poblaciones no inmunes, este ha sido la causa de grandes epidemias en todos los grupos de edad y se han notificado brotes esporádicos entre adultos y ancianos hospitalizados. Sin embargo, hay poca información sobre las verdaderas tasas de prevalencia e incidencia de las infecciones por rotavirus. La máxima incidencia se produce en los meses más fríos tanto en los climas templados como en los tropicales. Las infecciones son menos frecuentes o de menor patogenicidad en medios rurales higiénicos donde la lactancia natural es prolongada. Como resultado de experimentos en animales, actualmente se contempla la inmunización de mujeres gestantes para reforzar los títulos de anticuerpos en la leche. Las posibilidades de vacunación empiezan a perfilarse como prometedoras, pero quedan varios problemas pertinentes que resolver. Hace falta determinar la edad óptima para la vacunación y todavía no se ha encontrado la cepa adecuada para la vacuna ni un método que produzca cepas humanas en cantidades suficientes para vacunación en masa. En Finlandia se ha empezado a estudiar la preparación de una vacuna oral a base de un rotavirus hetereilogo bovino, que ha dado resultados alentadores. El clonaje molecular reciente de genes de rotavirus es otra posibilidad para la producción de una cepa adecuada para la vacuna, que es una creciente necesidad, especialmente para los países en desarrollo.Os rotavirus sat) uma das principais causas de morbidade e mortalidade por diarreia entre lactantes c criancas pequenas em todas as partes do mundo, especialmente nos paises menos desenvolvidos. Esses microrganismos se reproduzem no epitello veloso do intestino delgado ocasionando diarreia por denudaeao, atrofia do vela e diminuicao da capacidade de absorcao dos enterocitos. Constituem urn genera separado dentro da familia dos Reoviridae e acredita-se que ma evolucao é consequencia de mudancas acumulativas provocadas por desvio, transposicao e interc'ambio de segmentos de ARN. Seu descrobimento foi tardio devido a suas exigencias quanto ao meio e aos sistemas de cultura, o que tambem dificultou seu desenvolvimento em condicOes experimentais. A utilizacao de tripsina como mediador da ruptura do polipeptido exterior da capside facilitou a cultura de cepas humanas mediante testes preliminares em leitoes histoculturas subseqiientes continuas em rins de macaco. Esse metodo permitiu cultivar cepas humanas de tipo silvestre. As cepas humanas de rotavirus foram classificadas em quatro serotipos e dois subgrupos corn a ajuda de tecnicas como a fixacao do complemento, hemaglutinagio por imuno-aderencia e imuno- absorcao enzimatica (ELISA). A electroforese em gel policrilamidico possibilita a tipificacao de cepas prevalecentes numa cornunidade ou meio especial durante um period° determinado, perrnitindo a identificacao a primeira vista do subgrupo antigeno pelo padrao de migracao dos segmentos de ARN. Entre os metodos de imunoteste para deteccao do antfgeno e anticorpo do rotavirus, atualmente prefere-se o ELISA e o radioimunoensaio de fase solida (RIA), que sao sensiveis e faceis. Recentemente, o novo procedimento de neutralizacao por reducao de placas simplificou a avaliacao dos anticorpos neutralizadores de determinados serotipos. Os principais propagadores do virus sao as criancas corn diarreia, que frequentemcntc transmitem uma infeccao leve o assintomatica a seus contatos. Embora a suscetibilidade do homem, ao contrario dos outros mamiferos, seja menor nos primeiros seis meses de vida, em grandes hospitals observarem-se casos freqiientes de recem-nascidos corn infeccao assintomatica, e em alguns paises notificaram-se surtos de diarreia grave. As salas de hospital sao ideals para a dispersao do virus, pela reduzida imunidade dos recem-nascidos e alta concentracao, estabilidade a resistencia do virus. Em populaceies nao imunes, tern lido a causa de grandes epidemias em todos os grupos de idade e notificaram-se surtos esporadicos entre adultos e anciaos hospitalizados. Todavia, ha poucas informacaes sobre as verdadeiras taxas de prevalencia e incidencia das infeccoes por rotavirus. A maxima incidencia ocorre nos meses mais frios canto nos climas temperados como nos tropicais. As infeegoes sao menos frequentes ou de menor patogenicidade em meios rurais higienicos onde a lactancia natural e mais prolongada. Como resultado de experimentos em animais, atualmente considera- se a imunizacao de gestantes para reforcar os titulos de anticorpos no kite. As possihilidades de vacinacao comecam a parg, cer promissoras, mas falta resolver varios problemas pertinentes. Falta determinar a idade otima para a vacinagao e ainda nao se encontrou a cepa adequada para a vacina nem urn metodo que produza cepas humanas em quantidade suficiente para vacinacao em massa. Na Einlandia comecou-se a estudar a preparacio de uma vacina oral a base de um rotavirus bovino, corn resultados alentadores. A clonagem molecular recente de genes de rotavirus é outra possibilidade para a producao de uma cepa adequada para a vacina, que a uma crescente necessidade, especialmente para os paises em desenvolvimento.Universidad de Costa Rica. Instituto de Investigaciones en SaludUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

Investigación del INISA sobre la diarrea aguda del niño, estudios hospitalarios y comunitarios en Costa Rica 1976-1984

Artículo científico -- Universidad de Costa Rica. Instituto de Investigaciones en Salud, 1985Actualmente es posible detectar agentes entéricos potencialmente patógenos en más del 70% de los casos con diarrea aguda que requieren atención médica. Los rotavirus son responsables de casi la mitad de los casos, seguidos en importancia por ECET (toxina estable), Campylobacter, Shigella y Cryptospoidium. La rehidratación por via oral con solución de sales y azúcar es eficaz para rehidratar niños con diarrea de cualquier etiología. El hacinamiento, destete precoz y malas condiciones de higiene personal y ambiental son determinantes de la patogenicidad de rotavirus y otros agentes entéricos. En Puiscal, la patogenicidad es baja debido al ruralismo, lactancia materna prolongada y buena higiene. En amerindios. los rotavirus tampoco son frecuentes porque el ruralismo y la lactancia materna interfieren con la trasmisión del virus. El enfoque holístico es el indicado para controlar y prevenir la enfermedad diarreica de cualquier etiología, debiéndose reforzar programas de atención primaria de la salud, educación en salud y de saneamiento ambiental.Universidad de Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

Enteritis y colitis infecciosa del hombre

artículo -- Universidad de Costa Rica, Instituto de Investigaciones en Salud. 1982Most diarrheas affecting man in developing nations have an: infectious origin, and are transmitted from person to person or indirectly thorough water, food and utensils contaminated with the agents. About two thirds of all diarrheas observed in the community can be found associated with one or more agents, in excess of occurrence in matched controls. Rotaviruses and enterotoxigenic Escherichia coil are commonest in developing countries, followed by Shigella and Campylobacter fetus jejuni. In industrial nations, rotaviruses are the commonest, and enterotoxigenic bacteria very rare. Infants and young children are very susceptible, and suffer from severe attacks. The effect in children is a deterioration of the nutritional state (wasting and stunting); death may occur in severely dehidrated of toxic cases if proper assistance is not provided. Treatment consists in replacement of water and electrolyte losses by oral rehidration, and in administration of antimicrobial drugs, if justified. Breast-feeding is the most important defense mechanism to curtail incidence and to ameliorate symptoms particularly under poverty conditions. Prevention rests on improvement of education and environmental sanitation.Universidad de Costa Rica, Instituto de Investigaciones en Salud.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

Infectious agents in acute and chronic diarrhea of chilhood

Capítulo de libro -- Universidad de Costa Rica, Instituto de Investigaciones en Salud. 1984Even today acute diarrheal disease is thought of by many laymen as well as by some medical professionals in developing countries as being a syndrome of alimentary origin. Despite recognition of shigellosis, cholera, salmonellosis, giardiasis, amebiasis, and other enteric infectious diseases, there has been much difficulty in accepting the fact that most of the "nonspecific" diarrheas in the general population were also of an infectious nature. The frequent appearance of diarrhea after onset of weaning in many animal species and in man (1) and the systematic failure in the past to find pathogenic agents in a majority of the diarrheas tended to rule out a microbial etiology. Epidemiologists, pediatricians, and microbiologists suspected that the nonspecific diarrheas of childhood were also of microbial or viral origin (2) because of their characteristics in poor urban and rural settings. First, in such ecosystems, diarrhea prevails if sanitation and personal hygiene are deficient. Second, infants and preschool children are more frequently and more severely affected than school children, adolescents, and adults, which stiggests the acquisition of immunity and host resistance. Third, acute diarrhea in the community follows a pattern similar to that of other infectious diseases in that secondary cases develop after contact with the index case, eventually resulting in self-limiting to extensive outbreaks or even epidemics of great magnitude. It is clear that if personal hygiene and environmental sanitation are deficient, diarrhea is prevalent. This explains the similarity in diarrhea morbidity and mortality between some contemporary developing nations and New York City at the turn of the century, when environmental conditions in New York were as deficient as they are today in some developing nations.Universidad de Costa Rica. Instituto de Investigaciones en SaludUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

Rotavirus y campylobacter fetus jejuni asociados a un brote de diarrea en terneros

artículo -- Universidad de Costa Rica. Instituto de Investigaciones en Salud, 1984Rotaviruses and Campylobacter fetus jejuni are ubiquitous agents of diarrheal disease in animals and humans. Under natural conditions they do not seem to cross inter-species barriers; a zoonosis has not been documented for man. However, animal rotaviruses might contribute to the emergence of new reassortment strains in view of their segmented genome, and thus, produce new antigenic variants. On the contrary, Campylobacter fetus jejuni produces a true zoonosis. Man acquires bacilli by ingesting water and foodstuffs contaminated with feces from infected animals. In an outbreak of diarrhea in 22 calves, rotavirus was detected in 8 (36%) and Campylobacter in 6 (27%). Three (14%) calves experienced double infection. There were no human cases involved in this outbreak.Universidad de Costa Rica. Instituto de Investigaciones en SaludUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

Diarrea por Campylobacter fetus jejuni y otros agentes infecciosos en niños del área rural de Puriscal, Costa Rica

artículo -- Universidad de Costa Rica. Instituto de Investigaciones en Salud, 1984Between September 1979 and September 1981 a field study was conducted on the etiology of diarrhea' disease in the area of Puriscal, Costa Rica. The presence of enteric pathogens was investigated in the stools of 267 diarrheic children and 190 healthy controls. Both soups belong to yearly cohorts recruited at birth as part of a longitudinal multidisciplinary study of mothers and children. Campylobacter fetus lefuni was identified as the only pathogen in the stools of 24 diarrheic children (9%) and in four healthy controls (2% ), a significant difference (p< 0,05). The clinical features of the episodes were: irritability (77%), blood in stools (35%), anorexia (38,5%), and fever and vomiting (36%). Dehydration was not important among infected children (only one with 5% dehydration). All children received oral salt solutions and only two were treated with antibiotics. Rotaviruses were the main etiologic agents (17%) and Campylobacter ranked second (10,5% ). The frecuency of enterotoxigenic Enterobacteriaceae was similar in sick children and in controls (10%and 12%respectively).Entre setiembre de 1979 y setiembre de 1981, estudiamos 267 niños con diarrea aguda y 190 testigos, con el objeto de determinar la etiología y evaluar la importancia de Campylobacter fetus jejuni como agente etiológico y su influencia sobre el estado nutritional. Todos los niños tenían entre 0 y 24 meses de edad y pertenecen a las falanges anuales de un estudio longitudinal que realiza el INISA en el cantón de Puriscal, Costa Rica. Campylobacter fue el único agente en 24 niños con diarrea (9% ) y en cuatro niños sanos (2% ), encontrándose una diferencia significativa entre ambos grupos (x 2 = 9,05; p < 0,05). Además, se le encontró asociado a rotavirus o enterobacteriáceas toxigénicas en cuatro niños enfermos (1,5% ) y en dos testigos (1% ). El cuadro clínico se caracterizó por la evacuación de cinco a diez deposiciones líquidas al día, con sangre visible macroscópicamente en 39% de los casos. Los niños mostraron irritabilidad (77% ), anorexia (38,5% ), fiebre (36%) y vómitos (36%). Solo un niño presentó deshidratación del 5% y únicamente dos recibieron antibioticoterapia. El resto de los niños se recuperó satisfactoriamente mediante la administración de SUERORAL. El principal agente etiologico fue el rotavirus (17% ), seguido de Campylobacter (10,5%). La frecuencia de enterobacteriáceas toxigénicas fue similar en niños con diarrea y testigos (10% y 12% respectivamente).Universidad de Costa Rica, Instituto de investigaciones en SaludUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

Diarrhea associated with rotaviruses, enterotoxigenic Escherichia coli, Campylobacter, and other agents in costa rican children, 1976-1981

artículo -- Universidad de Costa Rica. Instituto de Investigaciones en Salud, 1983Rotaviruses, enterotoxigenic Escherichia coil, Salmonella, Shigella, and parasites were investigated in outpatient diarrheic children, and in hospitalized diarrheic and nondiarrheic children, between January 1976 and June 1979. In outpatient cases studied within 4 days of onset of symptoms, rotaviruses were the most common agents (45.3%); E. coil heatstable enterotoxin ranked second (13.4%); Shigella was third (8.1%); Salmonella was fourth (7.3%). In 63.2%, one or more enteric agents were detected. In hospitalized non-diarrheic children, asymptomatic shedding of pathogens was rarely observed. A later survey of outpatient diarrheic children revealed Campylobacter fetus jejuni in 8%. In 5.5 years of observation rotaviruses were endemic with excess frequency in the dry and cooler months of December and January. The excess occurrence of bacterial pathogens did not coincide with that of rotaviruses.Universidad de Costa Rica, Instituto de investigaciones en Salud.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

Low endemicity and low pathogenicity of rotaviruses among rural children in Costa Rica

Artículo científico -- Universidad de Costa Rica. Instituto de Investigaciones en Salud. 1985Rotaviruses were prospectively studied in 51 rural Costa Rican children from birth to two years. Samples of feces were collected weekly over a 33-month period. Rotavirus was detected in 45 (1.04%) of 4,317 fecal specimens; 39 infections were documented (an incidence of 0.5 infection per child-year), only five of which were associated with diarrhea (a pathogenicity of 12.8%). Secretory antibody in fecal extracts, detected in six of 39 infections, was short lived and did not protect against reinfection. Serum antibody was present in 69.6% of two-year-old children, but was not detected in 18.8% with documented infections. On the other hand, serum antibody was present in six of 14 children in whom rotavirus was not detected, thus increasing the overall incidence to 0.6 infection per child-year. The combination of prolonged breast-feeding, exposure to a lower infecting dose (compared with urban children), and a higher standard of hygiene than expected may explain the low incidence and low pathogenicity of rotavirus among these rural children.Universidad de Costa Rica. Instituto de Investigaciones en Salud.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

Anti-rotavirus antibody in human colostrum

reporte de investigación -- Universidad de Costa Rica, Instituto de Investigaciones en Salud. 1978. Una página. Este documento es privado debido a limitaciones de derechos de autor.During investigation of the epidemiology of human rotavirus infection in Costa Rica, the anti-human rotavirus capacity of colostrum was studied. We were looking for an explanation for the relatively low incidence of acute diarrhoeal disease among exclusively breast-fed infants. Colostrum was obtained, 1-76 h post partum, from thirty-three women aged 16-27 y from San José, the capital of Costa Rica, a city of about half a million inhabitants.Universidad de Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

Fecal rotaviruses, adenoviruses, corona virus like particles, and small round viruses in a cohort of rural costa rican children

Artículo científico -- Universidad de Costa Rica. Instituto de Investigaciones en Salud, 1985. Este documento es privado debido limitaciones de derechos de autor.Excretion patterns of fecal viruses were studied in a cohort of 51 rural Costa Rican children. The presence of rotavirus, adenovirus, coronavirus-like particles, and small round viruses was investigated by electron microscopy (EM) in 2,516 extracts of weekly fecal specimens. Rotavirus was in addition studied with ELISA. The incidence of diarrhea was 0.7 episodes per child-year. Rotavirus was the most common virus (0.53 infection/ child-year), followed by adenovirus (0.46 infection/child-year), and coronavirus-like particles (0.24 infection/child-year). However, the pathogenicity of rotavirus and adenovirus was low: only 3 of 24 rotavirus infections and 2 of 21 adenovirus infections were associated with diarrheal illness (12.5% and 9.5%, respectively). Small round viruses were detected in 23 specimens, but could not be assigned to a particular group of viruses. Children who excreted coronavirus-like particles and small round viruses were asymptomatic. Typical Norwalk-like viruses, astrovirus or calicivirus were not encountered. Rural conditions, good hygiene and prolonged breast feeding may explain the reduced exposure and pathogenicity of viral enteropathogens in rural Costa Rica.Universidad de Costa Rica, Instituto de Investigaciones en SaludUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA