Browsing by Author "Vial, Cecilia"

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    A 19 Year Analysis of Small Mammals Associated with Human Hantavirus Cases in Chile
    (2019) Torres-Perez, Fernando; Eduardo Palma, R.; Boric-Bargetto, Dusan; Vial, Cecilia; Ferres, Marcela; Vial, Pablo A.; Martinez-Valdebenito, Constanza; Pavletic, Carlos; Parra, Alonso; Marquet, Pablo A.; Mertz, Gregory J.
    Small mammals present in areas where hantavirus cardiopulmonary syndrome (HCPS) cases had occurred in central and southern Chile were captured and analyzed to evaluate the abundance of rodents and seroprevalence rates of antibodies to Andes orthohantavirus (ANDV). Sampling areas ranged from the Coquimbo to Aysen regions (30-45 degrees S approx.) regions. Ninety-two 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 degrees S), and the highest number of HCPS cases was registered in the Aysen 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.
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    A Single-Nucleotide Polymorphism of (V3) Integrin Is Associated with the Andes Virus Infection Susceptibility
    (2019) Martinez Valdebenito, Constanza Pamela; Angulo Troncoso Jenniffer Alexandra; Le Corre Pérez, Monique Nicole; Marco Caceres, Claudia Alejandra; Vial, Cecilia; Miquel Poblete, Juan Francisco; Cerda Lorca, Jaime Rodrigo; Mertz, Gregory; Vial, Pablo; Lopez Lastra, Marcelo Andres; Ferres Garrido, Marcela Viviana
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    Adaptation to Extreme Environments in an Admixed Human Population from the Atacama Desert
    (2019) Vicuña, Lucas; Fernández, Mario I.; Vial, Cecilia; Valdebenito, Patricio; Chaparro, Eduardo; Espinoza, Karena; Ziegler, Annemarie; Bustamante, Alberto; Eyheramendy Duerr, Susana
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    Comparison of VSV Pseudovirus and Focus Reduction Neutralization Assays for Measurement of Anti-Andes orthohantavirusNeutralizing Antibodies in Patient Samples
    (2020) Vial, Cecilia; Whitaker, Annalis; Wilhelm, Jan; Ovalle, Jimena; Perez, Ruth; Valdivieso, Francisca; Ferres, Marcela; Martinez-Valdebenito, Constanza; Eisenhauer, Philip; Mertz, Gregory J.; Hooper, Jay W.; Botten, Jason W.; Vial, Pablo A.
    Andes orthohantavirus(ANDV) is the etiologic agent of hantavirus cardiopulmonary syndrome (HCPS), which has a case fatality rate around 35%, with no effective treatment or vaccine available. ANDV neutralizing antibody (NAb) measurements are important for the evaluation of the immune response following infection, vaccination, or passive administration of investigational monoclonal or polyclonal antibodies. The standard assay for NAb measurement is a focus reduction neutralization test (FRNT) featuring live ANDV and must be completed under biosafety level (BSL)-3 conditions. In this study, we compared neutralization assays featuring infectious ANDV or vesicular stomatitis virus (VSV) pseudovirions decorated with ANDV glycoproteins for their ability to measure anti-ANDV NAbs from patient samples. Our studies demonstrate that VSV pseudovirions effectively measure NAb from clinical samples and have greater sensitivity compared to FRNT with live ANDV. Importantly, the pseudovirus assay requires less labor and sample materials and can be conducted at BSL-2.
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    Deletions in Genes Participating in Innate Immune Response Modify the Clinical Course of Andes Orthohantavirus Infection
    (2019) Esteves Ribeiro, Grazielle; Edgardo Leon, Luis; Perez, Ruth; Cuiza, Analia; Agustin Vial, Pablo; Ferres, Marcela; Mertz, Gregory J.; Vial, Cecilia
    Andes orthohantavirus (ANDV) is an important human pathogen causing hantavirus cardiopulmonary syndrome (HCPS) with a fatality rate of 30% in Chile. Around 60% of all cases have a severe clinical course, while the others have a mild clinical course. The main goal of this study was to understand if the genetic variation of patients is associated with the clinical course they develop after ANDV infection. For this, the frequency of copy number variants (CNVs, i.e., deletions and duplications) was studied in 195 patients, 88 with mild and 107 with severe HCPS. CNVs were called from intensity data of the Affymetrix Genome-Wide SNP Array 6.0. The analysis of the data was performed with PennCNV, ParseCNV and R softwares; Results: a deletion of 19, 416 bp in the q31.3 region of chromosome 1 is found more frequently in severe patients (p < 0.05). This region contains Complement Factor H Related (CFHR1) and CFHR3 genes, regulators of the complement cascade. A second deletion of 1.81 kb located in the p13 region of chr20 was significantly more frequent in mild patients (p < 0.05). This region contains the SIRPB1 gene, which participates in the innate immune response, more specifically in neutrophil trans-epithelial migration. Both deletions are associated with the clinical course of HCPS, the first being a risk factor and the second being protective. The participation of genes contained in both deletions in ANDV infection pathophysiology deserves further investigation.
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    Eco-epidemiology of rodent-associated trombiculid mites and infection with Orientia spp. in Southern Chile
    (2023) Silva de la Fuente, Maria Carolina; Perez, Caricia; Martinez-Valdebenito, Constanza; Perez, Ruth; Vial, Cecilia; Stekolnikov, Alexandr; Abarca, Katia; Weitzel, Thomas; Acosta-Jamett, Gerardo
    BackgroundScrub typhus is a potentially severe infection caused by bacteria of the genus Orientia, endemic in Asia-Pacific and recently discovered in southern Chile. The presented study aimed to determine the prevalence and species richness of rodent-associated trombiculid mites and their infection with Orientia spp. in different areas of two regions in southern Chile. Methodology/Principal findingsDuring summer 2020, trombiculid mites were collected from rodents captured in three areas in southern Chile known to be endemic for scrub typhus (Cochamo and Chiloe Island in the Los Lagos Region and Tortel in the Aysen Region). A total of 132 rodents belonging to five species were captured using Sherman-like traps; 89.4% were infested with trombiculids. Mite specimens were morphologically identified and subsequently tested by Orientia-specific qPCR. Six mite species were identified. Among chigger-infested rodents, 33.9% carried Orientia-positive mites; this rate was higher in Tortel (63.8%) than in Cochamo (45.0%) and Chiloe Island (2.0%). The analysis of individual mites (n = 901) revealed that 31.2% of Herpetacarus antarctica samples (n = 202) were positive for Orientia DNA; the prevalence was 7.0% in Paratrombicula neuquenensis (n = 213), 6.9% in Herpetacarus eloisae (n = 144), 3.6% in Argentinacarus expansus (n = 55), and 0% in Paratrombicula goffi (n = 110) and Quadraseta chiloensis (n = 177). The southernmost site (Tortel) showed the highest rates of trombiculid infestation, trombiculid load, and Orientia infection in the captured rodents. Conclusions/SignificanceOur study provides new insights into the trombiculid fauna and prevalence of Orientia in mites collected from wild rodents in southern Chile. Orientia DNA was detected in four of the six mite species. Rates of infestation, mite loads, and Orientia prevalences differed geographically and were highest in the Aysen Region. Our data improve our knowledge on possible vectors of scrub typhus and their distribution in Chile.
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    Genetic structure characterization of Chileans reflects historical immigration patterns
    (2015) Eyheramendy Duerr, Susana; Martínez, Felipe I.; Manevy, Federico; Vial, Cecilia; Repetto, Gabriela M.
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    Overcoming Health Inequities: Spatial Analysis of Seroprevalence and Vaccination Against COVID-19 in Chile
    (2024) Ramirez-Santana, Muriel; Correa, Juan; Franz, Loreto Nunez; Apablaza, Mauricio; Rubilar, Paola; Vial, Cecilia; Cortes, Lina Jimena; Hormazabal, Juan; Canales, Luis; Vial, Pablo; Aguilera, Ximena
    Background: In unequal economies, the spread of the first waves of the COVID-19 was usually associated with low socioeconomic status of individuals and their families. Chile exemplified this. By mid-2020, Chile had one of the highest SARS-CoV-2 infection rates in the world predominantly in poorer areas. A year later, the country launched a universal vaccination campaign based on the national strategy of immunization established in 1975. By 2022, Chile presented one of the highest COVID-19 vaccination coverages globally, reaching 94.3% of the population with the primary scheme by the end of 2022.Objective: This study analyzes the spatial distribution of SARS-CoV-2 seroprevalence at the beginning of the pandemic (2020) compared with the seroprevalence after 2 years of ongoing epidemic and COVID-19 vaccination campaigns (2022).Methods: Two population-based random samples of individuals aged 7 years and older from two Chilean cities were studied. Utilizing an enzyme-linked immunosorbent assay test, IgG antibodies were measured in serum of 1061 participants in 2020, and 853 in 2022.Results: Using the Global Moran's Index, the seroprevalence distribution pattern for the year 2020 showed clustering in the two cities. Conversely, seroprevalence and vaccinations were homogeneously distributed in 2022. These results show the success of the vaccination campaign in Chile, not only in coverage but also because it widely reached all individuals.Conclusions: The uptake of this preventive measure is high, regardless of the social and economic factors, achieving broad population immunity. The extensive deployment of the primary health care network contributed to reducing health inequities and promoting to universal health access.
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    Platelet Count in Patients with Mild Disease at Admission is Associated with Progression to Severe Hantavirus Cardiopulmonary Syndrome
    (2019) Lopez, Rene; Vial, Cecilia; Graf, Jeronimo; Calvo, Mario; Ferres, Marcela; Mertz, Gregory; Cuiza, Analia; Agueero, Begonia; Aguilera, Dante; Araya, Diego; Pailamilla, Ignacia; Paratori, Flavia; Torres-Torres, Victor; Vial, Pablo A.; Abarca, Juan; Miguel Noriega, Luis; Valdivieso, Francisca; Delgado, Iris; Martinez, Constanza; Carlos Chamorro, Juan; Hernandez, Jury; Pino, Marcelo; Vega, Ivonne; Otarola, Irisol; Ortega, Carlos; Daube, Elizabeth; Castillo, Constanza; Mardones, Jovita; Sanhueza, Ligia; Inostroza, Jaime; Donoso, Solange; Navarrete, Maritza; Araneda, Andres; Aguilera, Teresa; Osorio, Carola; Yobanolo, Veronica; Scholz, Luis; Riquelme, Raul; Riquelme, Mauricio; Munoz, Miriam
    Background: 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/mm(3), 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 /mm(3) 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.
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    Post-COVID-19 condition: a sex-based analysis of clinical and laboratory trends
    (2024) Delfino, Carlos; Poli, M. Cecilia; Vial, Cecilia; Vial, Pablo A.; Martinez, Gonzalo; Riviotta, Amy; Arbat, Catalina; Mac-Guire, Nicole; Hoppe, Josefina; Carvajal, Cristobal; Venturelli, Paula Munoz
    Background and aim Post-COVID-19 condition (PCC) encompasses long-lasting symptoms in individuals with COVID-19 and is estimated to affect between 31-67% of patients, with women being more commonly affected. No definitive biomarkers have emerged in the acute stage that can help predict the onset of PCC, therefore we aimed at describing sex-disaggregated data of PCC patients from a local cohort and explore potential acute predictors of PCC and neurologic PCC. Methods A local cohort of consecutive patients admitted with COVID-19 diagnosis between June 2020 and July 2021 were registered, and clinical and laboratory data were recorded. Only those <65 years, discharged alive and followed up at 6 and 12 months after admission were considered in these analyses. Multivariable logistic regression analysis was performed to explore variables associated with PCC (STATA v 18.0). Results From 130 patients in the cohort, 104 were contacted: 30% were women, median age of 42 years. At 6 months, 71 (68%) reported PCC symptoms. Women exhibited a higher prevalence of any PCC symptom (87 vs. 60%, p = 0.007), lower ferritin (p = 0.001) and procalcitonin (p = 0.021) and higher TNF levels (p = 0.042) in the acute phase compared to men. Being women was independently associated to 7.60 (95% CI 1.27-45.18, p = 0.026) higher risk for PCC. Moreover, women had lower return to normal activities 6 and 12 months. Conclusion Our findings highlight the lasting impact of COVID-19, particularly in young women, emphasising the need for tailored post-COVID care. The lower ferritin levels in women are an intriguing observation, warranting further research. The study argues for comprehensive strategies that address sex-specific challenges in recovery from COVID-19.
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    Proteinuria in Hantavirus Cardiopulmonary Syndrome: A Frequent Finding Linked To Mortality
    (2021) Lopez, Rene; Espinoza, Mauricio; Graf, Jeronimo; Mertz, Gregory; Ferres, Marcela; Calvo, Mario; Vial, Cecilia; Vial, Pablo A.
    Objectives: 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. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )
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    SARS-CoV-2 infectivity and antigenic evasion: spotlight on isolated Omicron sub-lineages
    (2024) Barrera, Aldo; Martinez-Valdebenito, Constanza; Angulo, Jenniffer; Palma, Carlos; Hormazabal, Juan; Vial, Cecilia; Aguilera, Ximena; Castillo-Torres, Pablo; Pardo-Roa, Catalina; Balcells, Maria Elvira; Nervi, Bruno; Le Corre, Nicole; Ferres, Marcela
    Since 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.
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    Single nucleotide variant at the αvβ3 integrin associated to Andes virus infection susceptibility
    (2018) Martinez Valdebenito, Constanza Pamela; Angulo Troncoso, Jenniffer Alexandra; Le Corre Perez, Monique Nicole; Marco Caceres, Claudia Alejandra; Vial, Cecilia; Miquel Poblete, Juan Francisco; Cerda Lorca, Jaime Rodrigo; Mertz, Gregory; Vial, Pablo; Lopez Lastra, Marcelo Andres; Ferres Garrido Marcela Viviana
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    Viral shedding and viraemia of Andes virus during acute hantavirus infection: a prospective study
    (2024) Ferres, Marcela; Martinez-Valdebenito, Constanza; Henriquez, Carolina; Marco, Claudia; Angulo, Jenniffer; Barrera, Aldo; Palma, Carlos; Pinto, Gonzalo Barriga; Cuiza, Analia; Ferreira, Leonila; Rioseco, Maria Luisa; Calvo, Mario; Fritz, Ricardo; Bravo, Sebastian; Bruhn, Alejandro; Graf, Jeronimo; Llancaqueo, Alvaro; Rivera, Gonzalo; Cerda, Carolina; Tischler, Nicole; Valdivieso, Francisca; Vial, Pablo; Mertz, Gregory; Vial, Cecilia; Le Corre, Nicole
    Background 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 -toperson 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 258 [95% CI 142-518]). 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 Investigaci & oacute;n y Desarrollo. Copyright (c) 2024 Elsevier Ltd. All rights reserved.