Browsing by Author "Ferres, Marcela"
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- ItemA 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.
- ItemAn Open One-Step RT-qPCR for SARS-CoV-2 detection(2024) Cerda, Ariel; Rivera, Maira; Armijo, Grace; Ibarra-Henriquez, Catalina; Reyes, Javiera; Blazquez-Sanchez, Paula; Aviles, Javiera; Arce, Anibal; Seguel, Aldo; Brown, Alexander J.; Vasquez, Yesseny; Cortez-San Martin, Marcelo; Cubillos, Francisco A.; Garcia, Patricia; Ferres, Marcela; Ramirez-Sarmiento, Cesar A.; Federici, Fernan; Gutierrez, Rodrigo A.The COVID-19 pandemic has resulted in millions of deaths globally, and while several diagnostic systems were proposed, real-time reverse transcription polymerase chain reaction (RT-PCR) remains the gold standard. However, diagnostic reagents, including enzymes used in RT-PCR, are subject to centralized production models and intellectual property restrictions, which present a challenge for less developed countries. With the aim of generating a standardized One-Step open RT-qPCR protocol to detect SARS-CoV-2 RNA in clinical samples, we purified and tested recombinant enzymes and a non-proprietary buffer. The protocol utilized M-MLV RT and Taq DNA pol enzymes to perform a Taqman probe-based assay. Synthetic RNA samples were used to validate the One-Step RT-qPCR components, demonstrating sensitivity comparable to a commercial kit routinely employed in clinical settings for patient diagnosis. Further evaluation on 40 clinical samples (20 positive and 20 negative) confirmed its comparable diagnostic accuracy. This study represents a proof of concept for an open approach to developing diagnostic kits for viral infections and diseases, which could provide a cost-effective and accessible solution for less developed countries.
- ItemAndes Virus Antigens Are Shed in Urine of Patients with Acute Hantavirus Cardiopulmonary Syndrome(AMER SOC MICROBIOLOGY, 2009) Godoy, Paula; Marsac, Delphine; Stefas, Elias; Ferrer, Pablo; Tischler, Nicole D.; Pino, Karla; Ramdohr, Pablo; Vial, Pablo; Valenzuela, Pablo D. T.; Ferres, Marcela; Veas, Francisco; Lopez Lastra, MarceloHantavirus cardiopulmonary syndrome (HCPS) is a highly pathogenic emerging disease (40% case fatality rate) caused by New World hantaviruses. Hantavirus infections are transmitted to humans mainly by inhalation of virus-contaminated aerosol particles of rodent excreta and secretions. At present, there are no antiviral drugs or immunotherapeutic agents available for the treatment of hantaviral infection, and the survival rates for infected patients hinge largely on early virus recognition and hospital admission and aggressive pulmonary and hemodynamic support. In this study, we show that Andes virus (ANDV) interacts with human apolipoprotein H (ApoH) and that ApoH-coated magnetic beads or ApoH-coated enzyme-linked immunosorbent assay plates can be used to capture and concentrate the virus from complex biological mixtures, such as serum and urine, allowing it to be detected by both immunological and molecular approaches. In addition, we report that ANDV-antigens and infectious virus are shed in urine of HCPS patients.
- ItemApOH-capture technology enhances Andes hantavirus detection allowing virus concentration from plasma and urine samples of patients with acute hantavirus cardiopulmonary syndrome(ELSEVIER SCIENCE BV, 2008) Godoy Mayorga, Paula Carolina; Stefas, Elias; Ferrer, Pablo; Vollrath, Valeska; Vial, Pablo; Ferres, Marcela; Veas, Francisco; Lopez Lastra, Marcelo
- ItemAutoantibodies against type I IFNs in patients with critical influenza pneumonia(2022) Zhang, Qian; Pizzorno, Andres; Miorin, Lisa; Bastard, Paul; Gervais, Adrian; Le Voyer, Tom; Bizien, Lucy; Manry, Jeremy; Rosain, Jeremie; Philippot, Quentin; Goavec, Kelian; Padey, Blandine; Cupic, Anastasija; Laurent, Emilie; Saker, Kahina; Vanker, Martti; Saerekannu, Karita; Garcia-Salum, Tamara; Ferres, Marcela; Le Corre, Nicole; Sanchez-Cespedes, Javier; Balsera-Manzanero, Maria; Carratala, Jordi; Retamar-Gentil, Pilar; Abelenda-Alonso, Gabriela; Valiente, Adoracion; Tiberghien, Pierre; Zins, Marie; Debette, Stephanie; Meyts, Isabelle; Haerynck, Filomeen; Castagnoli, Riccardo; Notarangelo, Luigi D.; Gonzalez-Granado, Luis I.; Dominguez-Pinilla, Nerea; Andreakos, Evangelos; Triantafyllia, Vasiliki; Rodriguez-Gallego, Carlos; Sole-Violan, Jordi; Ruiz-Hernandez, Jose Juan; Rodriguez de Castro, Felipe; Ferreres, Jose; Briones, Marisa; Wauters, Joost; Vanderbeke, Lore; Feys, Simon; Kuo, Chen-Yen; Lei, Wei-Te; Ku, Cheng-Lung; Tal, Galit; Etzioni, Amos; Hanna, Suhair; Fournet, Thomas; Casalegno, Jean-Sebastien; Queromes, Gregory; Argaud, Laurent; Javouhey, Etienne; Rosa-Calatrava, Manuel; Cordero, Elisa; Aydillo, Teresa; Medina, Rafael A.; Kisand, Kai; Puel, Anne; Jouanguy, Emmanuelle; Abel, Laurent; Cobat, Aurelie; Trouillet-Assant, Sophie; Garcia-Sastre, Adolfo; Casanova, Jean-LaurentIn an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine.
- ItemCharacterization of Oral Immunity in Cases and Close Household Contacts Exposed to Andes Orthohantavirus (ANDV)(2020) Martinez-Valdebenito, Constanza; Andaur, Camila; Angulo, Jenniffer; Henriquez, Carolina; Ferres, Marcela; Le Corre, NicoleBackground: Andes orthohantavirus (ANDV) is the sole etiologic agent of Hantavirus Cardiopulmonary Syndrome in Chile and, until now, the only Hantavirus known to be transmitted by person-to-person route. The main risk of person-to-person transmission is to be a sexual partner of an index case, and deep kissing the main mechanism of infection. Experimental reports suggest that ANDV infection can be inhibited by some saliva components. Therefore, some host factors like saliva quality, could help to explain why some individuals do not become infected even though their exposure to the virus is high.
- ItemComparison 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.
- ItemDeletions 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, CeciliaAndes 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.
- ItemDevelopment and Characterization of a Highly Specific and Sensitive SYBR Green Reverse Transcriptase PCR Assay for Detection of the 2009 Pandemic H1N1 Influenza Virus on the Basis of Sequence Signatures(AMER SOC MICROBIOLOGY, 2011) Medina, Rafael A.; Rojas, Mark; Tuin, Astrid; Huff, Stephen; Ferres, Marcela; Martinez Valdebenito, Constanza; Godoy, Paula; Garcia Sastre, Adolfo; Fofanov, Yuriy; SantaLucia, John, Jr.The emergence and rapid spread of the 2009 H1N1 pandemic influenza virus showed that many diagnostic tests were unsuitable for detecting the novel virus isolates. In most countries the probe-based TaqMan assay developed by the U.S. Centers for Disease Control and Prevention was used for diagnostic purposes. The substantial sequence data that became available during the course of the pandemic created the opportunity to utilize bioinformatics tools to evaluate the unique sequence properties of this virus for the development of diagnostic tests. We used a comprehensive computational approach to examine conserved 2009 H1N1 sequence signatures that are at least 20 nucleotides long and contain at least two mismatches compared to any other known H1N1 genome. We found that the hemagglutinin (HA) and neuraminidase (NA) genes contained sequence signatures that are highly conserved among 2009 H1N1 isolates. Based on the NA gene signatures, we used Visual-OMP to design primers with optimal hybridization affinity and we used ThermoBLAST to minimize amplification artifacts. This procedure resulted in a highly sensitive and discriminatory 2009 H1N1 detection assay. Importantly, we found that the primer set can be used reliably in both a conventional TaqMan and a SYBR green reverse transcriptase (RT)-PCR assay with no loss of specificity or sensitivity. We validated the diagnostic accuracy of the NA SYBR green assay with 125 clinical specimens obtained between May and August 2009 in Chile, and we showed diagnostic efficacy comparable to the CDC assay. Our approach highlights the use of systematic computational approaches to develop robust diagnostic tests during a viral pandemic.
- ItemDifferential neutralizing antibody responses elicited by CoronaVac and BNT162b2 against SARS-CoV-2 Lambda in Chile(2022) Acevedo, Monica L.; Gaete-Argel, Aracelly; Alonso-Palomares, Luis; de Oca, Marco Montes; Bustamante, Andres; Gaggero, Aldo; Paredes, Fabio; Cortes, Claudia P.; Pantano, Sergio; Martinez-Valdebenito, Constanza; Angulo, Jenniffer; Le Corre, Nicole; Ferres, Marcela; Navarrete, Marcelo A.; Valiente-Echeverria, Fernando; Soto-Rifo, RicardoThe SARS-CoV-2 Lambda variant has been prevalent in Latin America. An analysis of the neutralization capacity of antibodies elicited by CoronaVac and BNT162b2 against SARS-CoV-2 Lambda in plasma from healthcare workers and patients in Chile reveals that BNT162b2 elicits higher neutralizing antibody titres than CoronaVac.
- ItemDrug resistance mutations in proviral DNA of HIV-infected patients with low level of viremia(2020) Villalobos, Camila; Elena Ceballos, Maria; Ferres, Marcela; Palma, Carlos
- ItemFatal hemorrhagic pneumonia caused by human metapneumovirus in an immunocompetent child(2008) Donoso, Alejandro F.; Leon, Jose A.; Camacho, Jorge F.; Cruces, Pablo I.; Ferres, Marcela
- ItemFuente de infección de Bordetella pertussis en lactantes hospitalizados por coqueluche(SOC MEDICA SANTIAGO, 2011) Perret, Cecilia; Viviani, Tamara; Pena, Anamaria; Abarca, Katia; Ferres, MarcelaBackground: Despite pertussis vaccination, very young infants have the highest rates of morbidity and mortality caused by the microorganism. Aim: To determine the source of Pertussis infection in infants aged six months or less in Chile. Material and Methods: Twenty six household contacts of 10 young infants hospitalized with confirmed Pertussis were studied for the presence of Bordetella Pertussis by polymerase chain reaction (PCR). Clinical and demographic data were analyzed. Results: Respiratory symptoms were present in 20 (77%) contacts, being cough the most common. Pertussis cases were identified in every household and in 18 (72%) of the household members. Four members with B.pertussis were asymptomatic. Source of infection was identified in 80% (8/10) of the infant cases with ages ranging from 6 to 62 years. Half of primary cases had positive PR and their cough duration was significantly shorter compared to primary cases with negative PER. Conclusions: B. pertussis transmission to young infants occurred mainly within the household where adults are generally the source of the infection. Risk factors for infant infection are the same as in developed countries. Therefore, the same strategies, such as routine vaccination in adolescents and adults or cocoon strategy, will help to prevent this disease in infants. (Rev Med Chile 2011; 139: 448-454).
- ItemFunctional and Structural Analysis of the Internal Ribosome Entry Site Present in the mRNA of Natural Variants of the HIV-1(PUBLIC LIBRARY SCIENCE, 2012) Vallejos, Maricarmen; Carvajal, Felipe; Pino, Karla; Navarrete, Camilo; Ferres, Marcela; Pablo Huidobro Toro, Juan; Sargueil, Bruno; Lopez Lastra, MarceloThe 5'untranslated regions (UTR) of the full length mRNA of the HIV-1 proviral clones pNL4.3 and pLAI, harbor an internal ribosomal entry site (IRES). In this study we extend this finding by demonstrating that the mRNA 5'UTRs of natural variants of HIV-1 also exhibit IRES-activity. Cap-independent translational activity was demonstrated using bicistronic mRNAs in HeLa cells and in Xenopus laevis oocytes. The possibility that expression of the downstream cistron in these constructs was due to alternative splicing or to cryptic promoter activity was ruled out. The HIV-1 variants exhibited significant 5'UTR nucleotide diversity with respect to the control sequence recovered from pNL4.3. Interestingly, translational activity from the 5'UTR of some of the HIV-1 variants was enhanced relative to that observed for the 5'UTR of pNL4.3. In an attempt to explain these findings we probed the secondary structure of the variant HIV-1 5'UTRs using enzymatic and chemical approaches. Yet subsequent structural analyses did not reveal significant variations when compared to the pNL4.3-5'UTR. Thus, the increased IRES-activity observed for some of the HIV-1 variants cannot be ascribed to a specific structural modification. A model to explain these findings is proposed.
- ItemHighly Differentiated, Resting Gn-Specific Memory CD8(+) T Cells Persist Years after Infection by Andes Hantavirus(PUBLIC LIBRARY SCIENCE, 2010) Manigold, Tobias; Mori, Andres; Graumann, Rebecca; Llop, Elena; Simon, Valeska; Ferres, Marcela; Valdivieso, Francisca; Castillo, Constanza; Hjelle, Brian; Vial, PabloIn man, infection with South American Andes virus (ANDV) causes hantavirus cardiopulmonary syndrome (HCPS). HCPS due to ANDV is endemic in Southern Chile and much of Argentina and increasing numbers of cases are reported all over South America. A case-fatality rate of about 36% together with the absence of successful antiviral therapies urge the development of a vaccine. Although T-cell responses were shown to be critically involved in immunity to hantaviruses in mouse models, no data are available on the magnitude, specificity and longevity of ANDV-specific memory T-cell responses in patients. Using sets of overlapping peptides in IFN-gamma ELISPOT assays, we herein show in 78 Chilean convalescent patients that Gn-derived epitopes were immunodominant as compared to those from the N- and Gc-proteins. Furthermore, while the relative contribution of the N-specific response significantly declined over time, Gn-specific responses remained readily detectable ex vivo up to 13 years after the acute infection. Tetramer analysis further showed that up to 16.8% of all circulating CD3(+)CD8(+) T cells were specific for the single HLA-B*3501-restricted epitope Gn(465-473) years after the acute infection. Remarkably, Gn(465-473)-specific cells readily secreted IFN-gamma, granzyme B and TNF-alpha but not IL-2 upon stimulation and showed a 'revertant' CD45RA(+)CD27(-)CD28(-)CCR7(-)CD127(-) effector memory phenotype, thereby resembling a phenotype seen in other latent virus infections. Most intriguingly, titers of neutralizing antibodies increased over time in 10/17 individuals months to years after the acute infection and independently of whether they were residents of endemic areas or not. Thus, our data suggest intrinsic, latent antigenic stimulation of Gn-specific T-cells. However, it remains a major task for future studies to proof this hypothesis by determination of viral antigen in convalescent patients. Furthermore, it remains to be seen whether Gn-specific T cells are critical for viral control and protective immunity. If so, Gn-derived immunodominant epitopes could be of high value for future ANDV vaccines.
- ItemImportancia de las imágenes y el diagnóstico etiológico en el paciente inmunocomprometido con afección del sistema nervioso central. Segunda parte(2011) Besomi Zubieta, Marcela Andrea; Ferres, Marcela; Bidart, TeresaWe present the case of a 12-year-old boy with acute lymphocytic leukemia who developed pneumonia and multiple brain infarcts compatible with acute necrotic encephalitis. The infectious disease screening tests revealed influenza A H1N1 virus, Staphylococcus aureus in broncho alveolar lavage, E. colt and galactomannan antigen in blood. CNS influenza associated complications are reviewed. This case highlights the importance of magnetic resonance imaging as a diagnostic tool in the assessment of immunocompromised patients with CNS compromise and the value of brain biopsy in the final identification of an infectious disease etiology.
- ItemIncubation period of hantavirus cardiopulmonary syndrome(CENTERS DISEASE CONTROL & PREVENTION, 2006) Vial, Pablo A.; Valdivieso, Francisca; Mertz, Gregory; Castillo, Constanza; Belmar, Edith; Delgado, Iris; Tapia, Mauricio; Ferres, MarcelaThe potential incubation period from exposure to onset of symptoms was 7-39 days (median 18 days) in 20 patients with a defined period of exposure to Andes virus in a high-risk area. This period was 14-32 days (median 18 days) in 11 patients with exposure for <= 48 hours.
- ItemKinetic of humoral response induced by SARS-CoV-2 infection in convalescent plasma receptors and donors(WILEY, 2021) Barrera, Aldo; Martinez Valdebenito, Constanza; Rojas Orellana, Luis; Vizcaya Altamirano, Cecilia; Elena Ceballos, Maria; Pereira, Jaime; Chang, Mayling; Mondaca, Sebastian; Sarmiento, Mauricio; Ross, Patricio; Henriquez, Carolina; Nervi, Bruno; Ferres, Marcela; Balcells, Elvira; Le Corre, Nicole
- ItemMonkeypox Virus in Wastewater Samples from Santiago Metropolitan Region, Chile(2023) Ampuero, Manuel; Martinez-Valdebenito, Constanza; Ferres, Marcela; Soto-Rifo, Ricardo; Gaggero, AldoSewage surveillance provides useful epidemiologic and public health information on viral infections at the population level. We detected monkeypox virus DNA from sewage samples covering 85% of the population in Santiago Metropolitan Region, Chile. We also isolated infective viruses from those samples. Wastewater surveillance could complement clinical surveillance for monkeypox virus.
- ItemPlatelet 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, MiriamBackground: 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.