Browsing by Author "Castillo, Constanza"

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    High-dose intravenous methylprednisolone for hantavirus cardiopulmonary syndrome in Chile : a double-blind, randomized controlled clinical trial
    (2013) Vial, Pablo A.; Valdivieso, Francisca; Ferrés Garrido, Marcela Viviana; Riquelme, Raúl; Rioseco, M. Luisa; Calvo, Mario; Castillo, Constanza; Díaz, Ricardo; Scholz, Luis; Cuiza, Analia
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    Highly 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, Pablo
    In 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.
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    Incubation 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, Marcela
    The 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.
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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.