Browsing by Author "Medina, Rafael"

Now showing 1 - 16 of 16
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    Caracterización clínica y epidemiológica de infección asociada a atención en salud por virus influenza en pacientes críticos
    (2019) Gutiérrez, Valentina; Cerda, Jaime; Le Corre Pérez, Monique Nicole; Medina, Rafael; Ferrés Garrido, Marcela Viviana
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    Clinical and epidemiological characteristics of SARS-CoV-2 virus in ambulatory children under 2 years old
    (2022) Pérez, Carolina A.; Ormazábal, Ivana; Pérez Valenzuela, Javier; Araya del Pino, Andrea Paz; Medina, Rafael; Perret Pérez, Cecilia
    Background: SARS-CoV-2 is an emerging virus that has mainly affected adults; hence, most clinical information has been derived from that population. Most pediatric cases are mild and with nonspecific symptoms requiring outpatient management. Children are a major source of spread for most traditional respiratory viruses. Their role in SARS-CoV-2 transmission was thought to be relevant. Children under the age of two comprise a group that is more susceptible to infection since vaccines have not been approved for them until recently. The knowledge of clinical manifestation of COVID-19 in young children is scarce. Objectives: To describe the clinical, epidemiological, and demographic characteristics of children under 2 years old with confirmed COVID-19, who did not require hospitalization. Methods: This descriptive study was performed from May, 2020 to June, 2021. Children ages 0-2 years with COVID-19, confirmed by transcriptase-polymerase chain reaction assay that were performed in laboratories of the Red de Salud UC CHRISTUS Health Network, were selected to be contacted. If the parents accepted participating and their children were not hospitalized, a survey was sent to the patients' caregivers. Results: Of the 242 cases, 159 caregivers answered the survey (65.7%). The median age of the subjects was 14 months, and 53.5% were males. Fifty percent had comorbidities, of which one third corresponded to atopy. Ninety eight percent were secondary cases. Most of them were infected within their households (81%). The most frequent sources were their parents, followed by their grandparents. The most common symptom was fever (78%) followed by irritability (67.3%), rhinorrhea (66%), and fatigue (64.8%). Infants less than 6 months old more often presented with conjunctival congestion and less loss of appetite compared to older children (p < 0.05). Conclusions: This study provides valuable insights regarding COVID-19 in ambulatory young children. Most cases of SARS-CoV-2 infection in children under 2 years old do not require hospitalization. There was a slight male predominance, and the majority had been infected within their households. SARS-CoV-2 infection should be suspected in children under 2 years old presenting with fever, irritability, fatigue, and rhinorrhea. Children with positive household contacts and fever should also be tested for COVID-19.
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    Development of a Reverse Genetic System for Infectious Salmon Anemia Virus : Rescue of Recombinant Fluorescent Virus by Using Salmon Internal Transcribed Spacer Region 1 as a Novel Promoter
    (2015) Toro-Ascuy, D.; Tambley, C.; Beltran, C.; Mascayano, C.; Sandoval, N.; Olivares, E.; Medina, Rafael; Spencer, E.; Cortez-San Martin, M.
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    Ecology, Genetic Diversity, and Phylogeographic Structure of Andes Virus in Humans and Rodents in Chile
    (2009) Medina, Rafael; Palma Vásquez, Ramón Eduardo; Ferrés Garrido, Marcela Viviana
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    Emergence and rapid dissemination of highly pathogenic avian influenza virus H5N1 clade 2.3.4.4b in wild birds, Chile.
    (SPRINGER INTERNATIONAL PUBLISHING AG, 2023) Ariyama, Naomi; Pardo-Roa, Catalina; Munoz, Gabriela; Aguayo, Carolina; Avila, Claudia; Mathieu, Christian; Brito, Barbara; Medina, Rafael; Johow, Magdalena; Neira, Victor
    In December 2022, HPAI H5N1 clade 2.3.4.4b emerged in Chile. We detected the virus in 93 wild bird samples and sequenced the whole genome of nine Chilean strains from pelicans and gulls. Phylogenetic analysis suggests at least two different HPAI viral clusters in South America.
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    First report and genetic characterization of Seneca Valley virus (SVV) in Chile
    (SPRINGER INTERNATIONAL PUBLISHING AG, 2022) Bennett, Benjamin; Urzua-Encina, Constanza; Pardo-Roa, Catalina; Ariyama, Naomi; Lecocq, Claudio; Rivera, Carlos; Badia, Catalina; Suarez, Paulina; Agredo, Michel; Aguayo, Carolina; Avila, Claudia; Araya, Hugo; Perez, Patricio; Berrios, Felipe; Aguero, Belen; Mendieta, Vanessa; Pituco, Edviges Maristela; de Almeida, Iassudara Garcia; Medina, Rafael; Brito, Barbara; Johow, Magdalena; Neira Ramirez, Victor
    Seneca Valley virus (SVV) is a non-enveloped RNA virus and the only member of the Senecavirus A (SVA) species, in the Senecavirus genus, Picornaviridae family. SVV infection causes vesicular lesions in the oral cavity, snout and hooves of pigs. This infection is clinically indistinguishable from trade-restrictions-related diseases such as foot-and-mouth disease. Other clinical manifestations include diarrhoea, anorexia, lethargy, neurological signs and mortality in piglets during their first week of age. Before this study, Chile was considered free of vesicular diseases of swine, including SVV. In April 2022, a suspected case of vesicular disease in a swine farm was reported in Chile. The SVV was confirmed and other vesicular diseases were ruled out. An epidemiological investigation and phylogenetic analyses were performed to identify the origin and extent of the outbreak. Three hundred ninety-five samples from 44 swine farms were collected, including faeces (208), oral fluid (28), processing fluid (14), fresh semen (61), environmental samples (80) and tissue from lesions (4) for real-time RT-PCR detection. Until June 2022, the SVV has been detected in 16 out of 44 farms, all epidemiologically related to the index farm. The closest phylogenetic relationship of the Chilean SVV strain is with viruses collected from swine in California in 2017. The direct cause of the SVV introduction has not yet been identified; however, the phylogenetic analyses suggest the USA as the most likely source. Since the virus remains active in the environment, transmission by fomites such as contaminated feed cannot be discarded. Further studies are needed to determine the risk of the introduction of novel SVV and other transboundary swine pathogens to Chile.
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    First report of porcine respirovirus 1 in South America
    (2020) Aguero, B.; Mena, J.; Berrios, F.; Tapia, R.; Salinas, C.; Dutta, J.; van Bakel, H.; Mor, S. K.; Brito, B.; Medina, Rafael; Neira, V.
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    Glycosylations in the Globular Head of the Hemagglutinin Protein Modulate the Virulence and Antigenic Properties of the H1N1 Influenza Viruses
    (2013) Medina, Rafael; Stertz, Silke; Manicassamy, Balaji; Zimmermann, Petra; Sun, Xiangjie; Albrecht, Randy A.; Uusi-Kerttula, Hanni; Zagordi, Osvaldo; Belshe, Robert B.; Frey, Sharon E.; Tumpey, Terrence M.; García Sastre, Adolfo
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    Infection of novel reassortant H1N2 and H3N2 swine influenza A viruses in the guinea pig model
    (2018) Medina, Rafael; Tapia, Rodrigo.; García, Victoria.; Mena, Juan.; Bucarey Vivanco, Sergio.; Neira, Víctor.
    Abstract Novel H1N2 and H3N2 swine influenza A viruses (IAVs) were identified in commercial farms in Chile. These viruses contained H1, H3 and N2 sequences, genetically divergent from IAVs described worldwide, associated with pandemic internal genes. Guinea pigs were used as human surrogate to evaluate the infection dynamics of these reassortant viruses, compared with a pandemic H1N1 virus. All viruses replicated and were shed in the upper respiratory tract without prior adaptation although H1N2 viruses showed the highest shedding titers. This could have public health importance, emphasizing the need to carry out further studies to evaluate the zoonotic potential of these viruses.Abstract Novel H1N2 and H3N2 swine influenza A viruses (IAVs) were identified in commercial farms in Chile. These viruses contained H1, H3 and N2 sequences, genetically divergent from IAVs described worldwide, associated with pandemic internal genes. Guinea pigs were used as human surrogate to evaluate the infection dynamics of these reassortant viruses, compared with a pandemic H1N1 virus. All viruses replicated and were shed in the upper respiratory tract without prior adaptation although H1N2 viruses showed the highest shedding titers. This could have public health importance, emphasizing the need to carry out further studies to evaluate the zoonotic potential of these viruses.Abstract Novel H1N2 and H3N2 swine influenza A viruses (IAVs) were identified in commercial farms in Chile. These viruses contained H1, H3 and N2 sequences, genetically divergent from IAVs described worldwide, associated with pandemic internal genes. Guinea pigs were used as human surrogate to evaluate the infection dynamics of these reassortant viruses, compared with a pandemic H1N1 virus. All viruses replicated and were shed in the upper respiratory tract without prior adaptation although H1N2 viruses showed the highest shedding titers. This could have public health importance, emphasizing the need to carry out further studies to evaluate the zoonotic potential of these viruses.Abstract Novel H1N2 and H3N2 swine influenza A viruses (IAVs) were identified in commercial farms in Chile. These viruses contained H1, H3 and N2 sequences, genetically divergent from IAVs described worldwide, associated with pandemic internal genes. Guinea pigs were used as human surrogate to evaluate the infection dynamics of these reassortant viruses, compared with a pandemic H1N1 virus. All viruses replicated and were shed in the upper respiratory tract without prior adaptation although H1N2 viruses showed the highest shedding titers. This could have public health importance, emphasizing the need to carry out further studies to evaluate the zoonotic potential of these viruses.
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    Long-lasting neutralizing antibody responses in SARS-CoV-2 seropositive individuals are robustly boosted by immunization with the CoronaVac and BNT162b2 vaccines
    (2021) Muena, Nicolás A.; García Salum, Tamara Cristal; Pardo Roa, Catalina; Serrano García, Eileen Francisca; Levicán Asenjo, Jorge Enrique; Avendaño, María José; Almonacid Cárdenas, Leonardo Iván; Valenzuela Galaz, Gonzalo Hernán; Poblete Cárdenas, Estefany Aracely; Strohmeier, Shirin; Salinas Ortíz, Erick David; Haslwanter, Denise; Dieterle, Maria Eugenia; Jangra, Rohit K.; Chandran, Kartik; González, Claudia; Riquelme Pérez, Arnoldo Javier; Krammer, Florian; Tischler, Nicole D.; Medina, Rafael
    The durability of circulating neutralizing antibody (nAb) responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their boosting by vaccination remains to be defined. We show that outpatient and hospitalized SARS-CoV-2 seropositive individuals mount a robust neutralizing antibody (nAb) response that peaks at days 23 and 27 post-symptom onset, respectively. Although nAb titers remained higher in hospitalized patients, both study groups showed long-lasting nAb responses that can persist for up to 12 months after natural infection. These nAb responses in previously seropositive individuals can be significantly boosted through immunization with two doses of the CoronaVac (Sinovac) or one dose of the BNT162b2 (BioNTech/Pfizer) vaccines, suggesting a substantial induction of B cell memory responses. Noteworthy, three obese previously seropositive individuals failed to mount a booster response upon vaccination, warranting further studies in this population. Immunization of naïve individuals with two doses of the CoronaVac vaccine or one dose of the BNT162b2 vaccine elicited similar levels of nAbs compared to seropositive individuals 4.2 to 13.3 months post-infection with SARS-CoV-2. Thus, this preliminary evidence suggests that both, seropositive and naïve individuals, require two doses of CoronaVac to ensure the induction of robust nAb titers.
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    Novel Avulaviruses in Penguins, Antarctica
    (2017) Neira, Víctor; Tapia, Rodrigo; Verdugo, Claudio; Barriga, Gonzalo; Mor, Sunil; Fei Fan Ng, Terry; García, Victoria; Del Río, José; Rodríguez, Pedro; Medina, Rafael; Briceño, Cristóbal; González Acuña, Daniel
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    Novel penguin Avian avulaviruses 17, 18 and 19 are widely distributed in the Antarctic Peninsula
    (2019) Olivares, F.; Tapia, R.; Galvez, C.; Meza, F.; Barriga, G.P.; Borrás Chávez, Renato Francisco; Mena-Vasquez, J.; Medina, Rafael; Neira, V.
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    Pandemic H1N1 Influenza Isolated from Free-Ranging Northern Elephant Seals in 2010 off the Central California Coast
    (2013) Goldstein, Tracey; Mena, Ignacio; Anthony, Simon J.; Medina, Rafael; Robinson, Patrick W.; Greig, Denise J.; Costa, Daniel P.; Lipkin, W. Ian; García-Sastre, Adolfo; Boyce, Walter M.
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    Quasispecies diversity and its role in the virulence of the human influenza A virus.
    (2019) Almonacid Cárdenas, Leonardo Iván; Medina, Rafael; Pontificia Universidad Católica de Chile. Facultad de Ciencias Biológicas
    El virus de influenza estacional infectan entre el 5 y el 15% de la población humana cada año, lo que resulta en ∼500,000 muertes en todo el mundo. El virus de influenza estacional está asociada con dos tipos de virus de influenza: A (IAV) y B (IBV). Los virus de influenza pertenecen a la familia de virus Orthomyxoviridae que tienen genomas de ARN de sentido negativo, monocatenarios y segmentados. La segmentación del genoma, permite que el virus intercambie segmentos enteros con otras cepas, lo que facilita los saltos zoonóticos y aumenta la evolución y diversidad viral. Además, debido su polimerasa es propensa a errores debido a su falta de capacidad de corrección, se puede generar una diversidad considerable durante la replicación viral, que genera cambios graduales de nucleótidos que pueden acumularse con el tiempo. Estas fuentes de diversidad son fundamentales para la evolución del virus de la influenza y se han relacionado con marcadores que aumentan la patogénesis. La aparición de cepas pandémicas, las epidemias anuales y las variantes resisitentes a antivirales son ejemplos de cómo la diversidad genética impacta en la virulencia del patógeno. La diversidad de IAV, su arquitectura segmentada, el tamaño de la población y las coinfecciones generan las condiciones para que puedan ocurrir interacciones entre variantes genéticas. En este contexto, la teoría de las cuasiespecies puede contribuir a nuestra comprensión de la dinámica que puede surgir durante las infecciones por IAV. Las cuasiespecies virales se definen como la colección de genomas virales relacionados, sujetos a procesos continuos de variación genética, competencia y selección de la distribución con mayor “fitness”. En el modelo propuesto, tales interacciones entre los miembros de una cuasiespecie alcanzan un estado donde coexisten en un cuasi equilibrio que, en general, beneficia a toda la población. El desarrollo y las mejoras de las tecnologías de secuenciación, generando lecturas más largas y mayor profundidad, brindan nuevas oportunidades para estudiar las cuasiespecies virales. La mayor parte de la investigación se ha centrado en la validación experimental de conceptos introducidos por la teoría de la quasiespecie (es decir, umbral de error, robustez mutacional); para el IAV no existe una descripción clara ni una definición pragmática de las cuasiespecies en el contexto de una infección natural y su posible papel en la patogénesis. En esta tesis, investigamos si la diversidad de cuasiespecies virales modulan la virulencia de IAV. En primer lugar, para comprender mejor la diferencia entre las variantes de virus desde un enfoque funcional, desarrollamos un pipeline bioinformático. El IAV es un patógeno que ha captado la atención de los investigadores durante décadas, y como resultado de eso, hay una cantidad importante y una gran variedad de información. Para la mayoría de sus proteínas se cuenta con una o más estructuras de cristalografía y hay descripciones precisas con evidencia experimental que asocian funciones a diferentes regiones de cada proteína. Nuestro pipeline utiliza esta información resaltando las diferencias de nucleótidos en comparación con una secuencia de consenso, lo que proporciona una mejor comprensión de las funciones de la proteína que podrían verse afectadas en comparación con la secuencia de consenso. En segundo lugar, utilizamos este pipeline para analizar las variantes virales observadas en las secuencias de IAV obtenidas de individuos graves. Esto nos permitió identificar un nuevo aminoácido en la NA que confiere resistencia al antiviral oseltamivir. También identificamos cambios en la HA que probablemente ayuden a evadir la inmunidad preexistente (respuestas de anticuerpos) en un sujeto en particular, lo que sugiere que se trata de una deriva antigénica intra-huésped. Además, estos cambios se detectaron como poblaciones mixtas en muestras secuenciales, lo que indica un cambio dinámico en el tiempo del genoma de IAV. Finalmente, describimos la diversidad de las cuasiespecies experimentalmente in vitro e in vivo en humanos. Usando una combinación de los métodos de secuenciación Illumina y PacBio, medimos las poblaciones virales durante el curso de la infección cuando el IAV se pasó en diferentes sustratos celulares hasta 10 veces. Nuestros análisis revelaron la presencia de un número limitado de variantes IAV, que fluctuaron a lo largo de los pasajes y las réplicas biológicas. La mayoría de las variaciones de un solo nucleótido (SNV) se encontraron a baja frecuencia y rara vez se compartieron entre las réplicas. Sin embargo, encontramos SNV que se fijaron en los ultimos pasajes y, casi siempre, conllevaron un cambio de aminoácidos. Los datos sugieren que, típicamente, había un único genotipo dominante. La diversidad genética se evaluó en individuos infectados con IAV pertenecientes a un grupo severo o a uno no severo. Nuestros análisis genómicos indican una tendencia a tener más SNV en el grupo severo que en el no severo. En el grupo severo, solo el 25% de los SNV fueron de ocurrencia única en un segmento, mientras que el 45% en los no severos, lo que sugiere una dinámica genética diferente entre los dos grupos. Al igual que lo sucedido in vitro, generalmente un genotipo es el dominante en cada paciente. Nuestros resultados indican que las diversidad en las cuasiespecies alcanzarón altos niveles en casos particulares, pero a modo general para cada segemento, no hubo diferencias en diversidad entre el grupo grave y el no grave. Adicionalmente, se encontraron haplotipos alternativos con alta frecuencia en experimentos in vitro e in vivo, pero según los datos obtenidos de los pasajes celulares, es muy probable que sea un estado transitorio. Por lo tanto, esta investigación contribuye a la comprensión de cómo se generan las cuasiespecies y sugiere que los factores del sustrato y / o huésped, probablemente contribuyan a la diversidad viral intrínseca y a la capacidad de replicación.
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    Symptom Profiles and Risk Factors for Hospitalization in Patients With SARS-CoV-2 and COVID-19 : A Large Cohort From South America
    (2020) Díaz Piga, Luis Antonio; García-Salum, T.; Fuentes López, Eduardo; Ferrés, Marcela; Medina, Rafael; Riquelme Pérez, Arnoldo