Browsing by Author "Ferrés, Marcela"
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Item A 19 Year Analysis of Small Mammals Associated with Human Hantavirus Cases in Chile(2019) Torrez-Pérez, Fernando; Palma, Eduardo; Boric-Bargetto, Dusan; Vial, Cecilia; Ferrés, Marcela; Vial, Pablo; Martínez-Valdebenito, Constanza; Pavletic, Carlos; Parra, Alonso; Marquet, Pablo; Mertz, GregorySmall mammals present in areas where hantavirus cardiopulmonary syndrome (HCPS) cases had occurred in central and southern Chile were captured and analyzed to evaluate theabundance of rodents and seroprevalence rates of antibodies to Andes orthohantavirus (ANDV). Sampling areas ranged from the Coquimbo to Aysén regions (30–45° S approx.) regions. Ninetytwo sites in peridomestic and countryside areas were evaluated in 19 years of sampling. An antibody against ANDV was detected by strip immunoassay in 58 of 1847 specimens captured using Sherman traps. Of the eleven species of rodents sampled, Abrothrix olivacea, Oligoryzomys longicaudatus and Abrothrix hirta were the most frequently trapped. O. longicaudatus had the highest seropositivity rate, and by logistic regression analysis, O. longicaudatus of at least 60 g had 80% or higher probability to be seropositive. Sex, age and wounds were significantly related to seropositivity only for O. longicaudatus. Across administrative regions, the highest seropositivity was found in the El Maule region (34.8–36.2° S), and the highest number of HCPS cases was registered in the Aysén region. Our results highlight the importance of long term and geographically extended studies, particularly for highly fluctuating pathogens and their reservoirs, to understand the implications of the dynamics and transmission of zoonotic diseases in human populations.Item A Single-Nucleotide Polymorphism of αVβ3 Integrin Is Associated with the Andes Virus Infection Susceptibility(2019) Martínez-Valdebenito, Constanza; Angulo, Jenniffer; Corre, Nicole Le; Marco, Claudia; Vial, Cecilia; Miquel, Juan Francisco; Cerda, Jaime; Mertz, Gregory; Vial, Pablo; Lopez-Lastra, Marcelo; Ferrés, MarcelaThe Andes Orthohantavirus (ANDV), which causes the hantavirus cardiopulmonary syndrome, enters cells via integrins, and a change from leucine to proline at residue 33 in the PSI domain (L33P), impairs ANDV recognition. We assessed the association between this human polymorphism and ANDV infection. We defined susceptible and protective genotypes as “TT” (coding leucine) and “CC” (coding proline), respectively. TT was present at a rate of 89.2% (66/74) among the first cohort of ANDV cases and at 60% (63/105) among exposed close-household contacts, who remained uninfected (p < 0.05). The protective genotype (CC) was absent in all 85 ANDV cases, in both cohorts, and was present at 11.4% of the exposed close-household contacts who remained uninfected. Logistic regression modeling for risk of infection had an OR of 6.2–12.6 (p < 0.05) in the presence of TT and well-known ANDV risk activities. Moreover, an OR of 7.3 was obtained when the TT condition was analyzed for two groups exposed to the same environmental risk. Host genetic background was found to have an important role in ANDV infection susceptibility, in the studied population.Item Factores de riesgo socio-demográficos del síndrome cardiopulmonar por hantavirus(2019) Vial, Cecilia; Valdivieso, Francisca; Cuiza, Analía; Delgado, Iris; Ribeiro, Grazielle; Llop, Elena; Ferrés, Marcela; Repetto, Gabriela; Riquelme, Raúl; Rioseco, María Luisa; Calvo, Mario; Mertz, Gregory; Vial, PabloBackground: Hantavirus cardiopulmonary syndrome (HCPS) is caused by new world hantaviruses, among which Andes hantavirus (ANDV) is endemic to Chile and Southern Argentina. The disease caused by ANDV produces plasma leakage leading to enhanced vascular permeability and has a high case fatality rate (35%), mainly due to respiratory failure, pulmonary edema and myocardial dysfunction, hypoperfusion and shock. Host sociodemographic and genetic factors might influence the course and outcome of the disease. Yet, they have not been thoroughly characterized. Aim: To evaluate sociodemographic factors as risk factors in severity of HCPS. Patients and Methods: Study period: 2004-20013, attending in eight collaborative centers, etiological diagnosis was performed by serology or molecular biology, mild and severe HCPS were compared.139 Chilean patients were analyzed, 64 (46%) with severe disease among which 12 (19 %) died. Results: European ethnicity had 5,1 times higher risk than Amerindian ethnic group to develop a severe HCPS, greater seriousness that was also associated with an urban residence. Conclusion: It was observed that ethnicity and type of residence were significant risk factors for HCPS severity. Hypotheses explaining these findings are discussed.Item Modelo computacional interactivo, semi-automatizado y de código abierto aplicado a la vigilancia de virus respiratorios(2020) Reyes, Felipe; Ferrés, Marcela; Vial, Pablo; Vollrath, Valeska; Camponovo, Rossanna; Montecinos, Luisa; Hirsch, Tamara; Valenzuela, Patricia; Perret, CeciliaLas infecciones respiratorias agudas (IRA) causadas por virus son una importante causa de morbilidad y mortalidad en el mundo, afectando principalmente a niños y adultos mayores. Se asocian a un alto número de consultas y hospitalizaciones, a una significativa sobrecarga del sistema de salud y a un alto costo económico. La vigilancia de virus respiratorios tiene el potencial de ayudar a optimizar la respuesta sanitaria, garantizar la disponibilidad de recursos humanos, racionalizar los recursos y disminuir los costos asociados a la atención en salud. Con el objetivo de optimizar la recolección y visualización de los datos de nuestro actual sistema de vigilancia de virus respiratorios, se diseñó una plataforma basada en R y sus paquetes Shiny, que permite la creación de una interfase web interactiva y amigable para la recolección, análisis y publicación de los datos. Se ingresaron a esta plataforma los datos de la red de vigilancia metropolitana de virus respiratorios disponibles desde 2006. En esta plataforma, el investigador demora menos de un minuto en registrar los datos. El análisis y publicación es inmediato, llegando a cualquier usuario con un dispositivo conectado a Internet, quien puede elegir las variables a consultar. Con un costo muy bajo, en poco tiempo y utilizando el lenguaje de programación R, se logró crear un sistema simple e interactivo, disminuyendo el tiempo de carga y análisis de datos de forma considerable, posiblemente aumentando el impacto y la disponibilidad de esta vigilanciaItem Mother-to-Child Transmission of Andes Virus through Breast Milk, Chile(2020-08) Ferrés, Marcela; Martínez-Valdebenito, Constanza; Angulo, Jenniffer; Henríquez, Carolina; Vera-Otaróla, Jorge; Vergara, María José; Pérez, Javier; Fernández, Jorge; Sotomayor, Viviana; Valdés, María Francisca; González-Candia, Diego; Tischler, Nicole D.; Vial, Cecilia; Vial, Pablo; Mertz, Gregory; Le Corre, NicoleAndes virus (ANDV) is the only hantavirus transmitted between humans through close contact. We detected the genome and proteins of ANDV in breast milk cells from an infected mother in Chile who transmitted the virus to her child, suggesting gastrointestinal infection through breast milk as a route of ANDV person-to-person transmission.Item Person-to-Person Household and Nosocomial Transmission of Andes Hantavirus, Southern Chile, 2011(Centers for Desease Control and Prevention, 2014) Martinez-Valdebenito, Constanza; Calvo, Mario; Vial, Cecilia; Mansilla, Rita; Marco, Claudia; Palma, Eduardo; Vial, Pablo; Valdivieso, Francisca; Mertz, Gregory; Ferrés, MarcelaAndes hantavirus (ANDV) causes hantavirus cardiopulmonary syndrome in Chile and is the only hantavirus for which person-to-person transmission has been proven. We describe an outbreak of 5 human cases of ANDV infection in which symptoms developed in 2 household contacts and 2 health care workers after exposure to the index case-patient. Results of an epidemiologic investigation and sequence analysis of the virus isolates support person-to-person transmission of ANDV for the 4 secondary case-patients, including nosocomial transmission for the 2 health care workers. Health care personnel who have direct contact with ANDV case-patients or their body fluids should take precautions to prevent transmission of the virus. In addition, because the incubation period of ANDV after environmental exposure is longer than that for person-to-person exposure, all persons exposed to a confirmed ANDV case-patient or with possible environmental exposure to the virus should be monitored for 42 days for clinical symptoms.Item Platelet Count in Patients with Mild Disease at Admission is Associated with Progression to Severe Hantavirus Cardiopulmonary Syndrome(2019) López, René; Vial, Cecilia; Graf, Jerónimo; Calvo, Mario; Ferrés, Marcela; Mertz, Gregory; Cuiza, Analía; Agüero, Begonia; Aguilera, Dante; Araya, Diego; Pailamilla, Ignacia; Paratori, Flavia; Torres-Torres, Víctor; Vial, Pablo; HantavirusStudy Group in ChileBACKGROUND: Hantavirus cardiopulmonary syndrome (HCPS) has a mortality up to 35-40% and its treatment is mainly supportive. A variable to predict progression from mild to severe disease is unavailable. This study was performed in patients with documented infection by Andes orthohantavirus, and the aim was to find a simple variable to predict progression to moderate/severe HCPS in patients with mild disease at admission. METHODS: We performed a retrospective analysis of 175 patients between 2001 and 2018. Patients were categorized into mild, moderate, and severe disease according to organ failure and advanced support need at hospital admission (e.g., mechanical ventilation, vasopressors). Progression to moderate/severe disease was defined accordingly. Clinical and laboratory variables associated with progression were explored. RESULTS: Forty patients with mild disease were identified; 14 of them progressed to moderate/severe disease. Only platelet count was different between those who progressed versus those that did not (37 (34-58) vs. 83 (64-177) K/mm3, p < 0.001). A ROC curve analysis showed an AUC = 0.889 (0.78-1.0) p < 0.001, with a platelet count greater than 115K /mm3 ruling out progression to moderate/severe disease. CONCLUSIONS: In patients with mild disease at presentation, platelet count could help to define priority of evacuation to tertiary care centers.Item Proteinuria in Hantavirus Cardiopulmonary Syndrome: A Frequent Finding Linked To Mortality(2021) López, René; Espinoza, Mauricio; Graf, Jerónimo; Mertz, Gregory; Ferrés, Marcela; Calvo, Mario; Vial, Cecilia; Vial, Pablo; Hantavirus Study Group in ChileObjectives: To determine the relative frequency and prognosis value of proteinuria in hantavirus cardiopulmonary syndrome (HCPS) due to Andes virus. Methods: This observational analytical study prospectively obtained data from patients admitted to 12 health centers in nine Chilean cities between 2001 and 2018. Only patients with confirmed Andes virus HCPS and laboratory characterization that included qualitative proteinuria determination at admission were considered. Results: The database involved 175 patients, 95 of them had a measurement of urine protein at the time of hospital admission. They were mainly male (71%) and the median age was 35 [22-47] years. Median duration of the febrile prodromal time was 5 [4-7] days. Hospital length of stay and hospital mortality rate were 10 [7-14] days and 21.1%, respectively. Seventy-three patients (77%) were identified with proteinuria at admission, which was associated with increased mortality rate (26% versus 5%, p=0.036) and the relative risk was 1.3 [1.1-1.6], p=0.002. Conclusions: Proteinuria is a frequent finding in patients with HCPS, which is associated with a higher mortality rate.Publication SARS-CoV-2 infectivity and antigenic evasion: spotlight on isolated Omicron sub-lineages(2024) Barrera, Aldo; Martínez, Constanza; Angulo, Jenniffer; Palma, Carlos; Hormazabal, Juan; Vial Cox, María Cecilia; Aguilera, Ximena; Castillo, Pablo; Pardo, Catalina; Balcells, María; Nervi, Bruno; Le Corre, Nicole; Ferrés, MarcelaSince the SARS-CoV-2 outbreak in 2019, a diversity of viral genomic variants has emerged and spread globally due to increased transmissibility, pathogenicity, and immune evasion. By the first trimester of 2023 in Chile, as in most countries, BQ and XBB were the predominant circulating sub-lineages of Omicron. The molecular and antigenic characteristics of these variants have been mainly determined using non-authentic spike pseudoviruses, which is often described as a limitation. Additionally, few comparative studies using isolates from recent Omicron sub-lineages have been conducted. In this study, we isolated SARS-CoV-2 variants from clinical samples, including the ancestral B.1.1, Delta, Omicron BA.1, and sub-lineages of BA.2 and BA.5. We assessed their infectivity through cell culture infections and their antibody evasion using neutralization assays. We observed variations in viral plaque size, cell morphology, and cytotoxicity upon infection in Vero E6-TMPRSS2 cells for each variant compared to the ancestral B.1.1 virus. BA.2-derived sub-variants, such as XBB.1.5, showed attenuated viral replication, while BA.5-derived variants, such as BQ.1.1, exhibited replication rates similar to the ancestral SARS-CoV-2 virus. Similar trends were observed in intestinal Caco-2 cells, except for Delta. Antibody neutralization experiments using sera from individuals infected during the first COVID-19 wave (FWI) showed a consistent but moderate reduction in neutralization against Omicron sub-lineages. Interestingly, despite being less prevalent, BQ.1.1 showed a 6.1-fold greater escape from neutralization than XBB.1.5. Neutralization patterns were similar when tested against sera from individuals vaccinated with 3xBNT162b2 (PPP) or Coronavac-Coronavac-BNT162b2 (CCP) schedules. However, CCP sera showed 2.3-fold higher neutralization against XBB.1.5 than FWI and PPP sera. This study provides new insights into the differences between BA.2 and BA.5-derived variants, leading to their eventual outcompetition. Our analysis offers important evidence regarding the balance between infectivity and antigenic escape that drives the evolution of second-generation SARS-CoV-2 variants in the population.Publication Viral shedding and viraemia of Andes virus during acute hantavirus infection: a prospective study(2024) Ferrés, Marcela; Martínez, Constanza; Henriquez, Carolina; Marco, Claudia; Barrera, Aldo; Palma, Carlos; Barriga, Gonzalo; Cuiza, Analia; Ferreira, Leonila; Rioseco, María; Calvo, Mario; Fritz, Ricardo; Bravo, Sebastián; Bruhn, Alejandro; Graf, Jerónimo; Llancaqueo, Alvaro; Rivera, Gonzalo; Cerda, Carolina; Tischler, Nicole; Valdivieso, Francisca; Vial, Pablo; Mertz, Gregory; Vial Cox, María Cecilia; Le Corre, NicoleBackground: Andes virus (ANDV) is a zoonotic Orthohantavirus leading to hantavirus cardiopulmonary syndrome. Although most transmissions occur through environmental exposure to rodent faeces and urine, rare person-to-person transmission has been documented, mainly for close contacts. This study investigates the presence and infectivity of ANDV in body fluids from confirmed cases and the duration of viraemia. Methods: In this prospective study, 131 participants with confirmed ANDV infection were enrolled in Chile in a prospective study between 2008 and 2022. Clinical samples (buffy coat, plasma, gingival crevicular fluid [GCF], saliva, nasopharyngeal swabs [NPS], and urine) were collected weekly for 3 weeks together with clinical and epidemiological data. Samples were categorised as acute or convalescent (up to and after 16 days following onset of symptoms). Infectivity of positive fluids was assessed after the culture of samples on Vero E6 cells and use of flow cytometry assays to determine the production of ANDV nucleoprotein. Findings: ANDV RNA was detected in 100% of buffy coats during acute phase, declining to 95% by day 17, and to 93% between days 23-29. ANDV RNA in GCF and saliva decreased from 30% and 12%, respectively, during the acute phase, to 12% and 11% during the convalescent phase. Successful infectivity assays of RT-qPCR-positive fluids, including GCF, saliva, NPS, and urine, were observed in 18 (42%) of 43 samples obtained during the acute phase of infection. After re-culture, the capacity to infect Vero E6 cells was maintained in 16 (89%) of 18 samples. Severity was associated with the presence of ANDV RNA in one or more fluids besides blood (odds ratio 2·58 [95% CI 1·42-5·18]). Interpretation: ANDV infection is a systemic and viraemic infection, that affects various organs. The presence of infectious particles in body fluids contributes to our understanding of potential mechanisms for person-to-person transmission, supporting the development of preventive strategies. Detection of ANDV RNA in additional fluids at hospital admission is a predictor of disease severity. Funding: National Institutes of Health and Agencia de Investigación y Desarrollo.