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Eco-epidemiology of rodent-associated trombiculid mites and infection with Orientia spp. in Southern Chile

2023 , María Carolina Silva de la Fuente , Caricia Pérez , Constanza Martínez-Valdebenito , Pérez Ball, Ruth , VIAL COX, MARIA CECILIA , Alexandr Stekolnikov , Katia Abarca , Gerardo Acosta-Jamett , WEITZEL, THOMAS , Jessica N. Ricaldi

Background Scrub 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 findings During summer 2020, trombiculid mites were collected from rodents captured in three areas in southern Chile known to be endemic for scrub typhus (Cochamó and Chiloé Island in the Los Lagos Region and Tortel in the Aysén 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 Cochamó (45.0%) and Chiloé 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/Significance Our 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 Aysén Region. Our data improve our knowledge on possible vectors of scrub typhus and their distribution in Chile.

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Chromosomal microarrays testing in children with developmental disabilities and congenital anomalies

2015 , GUILLERMO ROBERTO LAY SON RODRIGUEZ , Karena Espinoza , VIAL COX, MARIA CECILIA , Juan C. Rivera , María L. Guzmán , REPETTO LISBOA, MARIA GABRIELA

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SARS-CoV-2 infectivity and antigenic evasion: spotlight on isolated Omicron sub-lineages

2024 , Aldo Barrera , Constanza Martínez-Valdebenito , Jenniffer Angulo , Carlos Palma , HORMAZABAL CASTILLO, JUAN PATRICIO , VIAL COX, MARIA CECILIA , AGUILERA SANHUEZA, XIMENA PAZ , Pablo Castillo-Torres , Catalina Pardo-Roa , María Elvira Balcells , Bruno Nervi , Nicole Le Corre , Marcela Ferrés

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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Overcoming Health Inequities: Spatial Analysis of Seroprevalence and Vaccination Against COVID-19 in Chile

2024 , Muriel Ramírez-Santana , Juan Correa , Loreto Núñez Franz , APABLAZA SALINAS, MAURICIO IVÁN , RUBILAR RAMIREZ, PAOLA ANDREA , VIAL COX, MARIA CECILIA , CORTES SALINAS, LINA JIMENA , HORMAZABAL CASTILLO, JUAN PATRICIO , Luis Canales , VIAL CLARO, PABLO AGUSTIN , AGUILERA SANHUEZA, XIMENA PAZ

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Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19

2022 , Carmelo Carmona-Rivera , Yu Zhang , Kerry Dobbs , Tovah E. Markowitz , Clifton L. Dalgard , Andrew J. Oler , Dillon R. Claybaugh , Deborah Draper , Meng Truong , Ottavia M. Delmonte , Francesco Licciardi , Ugo Ramenghi , Nicoletta Crescenzio , Luisa Imberti , Alessandra Sottini , Virginia Quaresima , Chiara Fiorini , Valentina Discepolo , Andrea Lo Vecchio , Alfredo Guarino , Luca Pierri , Andrea Catzola , Andrea Biondi , Paolo Bonfanti , POLI HARLOWE, MARIA CECILIA BERTA , Yasmin Espinosa , Camila Astudillo , REY JURADO, EMMA , VIAL COX, MARIA CECILIA , Javiera de la Cruz , Ricardo Gonzalez , Cecilia Pinera , Jacqueline W. Mays , Ashley Ng , Andrew Platt , Beth Drolet , John Moon , Edward W. Cowen , Heather Kenney , Sarah E. Weber , Riccardo Castagnoli , Mary Magliocco , Michael A. Stack , Gina Montealegre , Karyl Barron , Danielle L. Fink , Douglas B. Kuhns , Stephen M. Hewitt , Lisa M. Arkin , Daniel S. Chertow , Helen C. Su , Luigi D. Notarangelo , Mariana J. Kaplan

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Hemodynamic and Pulmonary Permeability Characterization of Hantavirus Cardiopulmonary Syndrome by Transpulmonary Thermodilution

2019 , LOPEZ HERNANDEZ, RENE RAMON , Rodrigo Pérez-Araos , Álvaro Salazar , Ana L. Ulloa , VIAL COX, MARIA CECILIA , VIAL CLARO, PABLO AGUSTIN , GRAF SANTOS, JERÓNIMO

Hantavirus cardiopulmonary syndrome (HCPS) is characterized by capillary leak, pulmonary edema (PE), and shock, which leads to death in up to 40% of patients. Treatment is supportive, including mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO). Hemodynamic monitoring is critical to titrate therapy and to decide ECMO support. Transpulmonary thermodilution (TPTD) provides hemodynamic and PE data that have not been systematically used to understand HCPS pathophysiology. We identified 11 HCPS patients monitored with TPTD: eight on MV, three required ECMO. We analyzed 133 measurements to describe the hemodynamic pattern and its association with PE. The main findings were reduced stroke volume, global ejection fraction (GEF), and preload parameters associated with increased extravascular lung water and pulmonary vascular permeability compatible with hypovolemia, myocardial dysfunction, and increased permeability PE. Lung water correlated positively with heart rate (HR, r = 0.20) and negatively with mean arterial pressure (r = −0.27) and GEF (r = −0.36), suggesting that PE is linked to hemodynamic impairment. Pulmonary vascular permeability correlated positively with HR (r = 0.31) and negatively with cardiac index (r = −0.49), end-diastolic volume (r = −0.48), and GEF (r = −0.40), suggesting that capillary leak contributes to hypovolemia and systolic dysfunction. In conclusion, TPTD data suggest that in HCPS patients, increased permeability leads to PE, hypovolemia, and circulatory impairment.

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Post-COVID-19 condition: a sex-based analysis of clinical and laboratory trends

2024 , Carlos Delfino , POLI HARLOWE, MARIA CECILIA BERTA , VIAL COX, MARIA CECILIA , VIAL CLARO, PABLO AGUSTIN , Gonzalo Martínez , Amy Riviotta , Catalina Arbat , Nicole Mac-Guire , Josefina Hoppe , CARVAJAL BENAVIDES, CÉSAR CRISTÓBAL , MUÑOZ VENTURELLI, PAULA ANDREA

Background and aimPost-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.MethodsA 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).ResultsFrom 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.ConclusionOur 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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Genetic structure characterization of Chileans reflects historical immigration patterns

2015 , Susana Eyheramendy , Felipe I. Martinez , Federico Manevy , VIAL COX, MARIA CECILIA , REPETTO LISBOA, MARIA GABRIELA

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Platelet Count in Patients with Mild Disease at Admission is Associated with Progression to Severe Hantavirus Cardiopulmonary Syndrome

2019 , LOPEZ HERNANDEZ, RENE RAMON , Mario Calvo , VIAL COX, MARIA CECILIA , Marcela Ferrés , GRAF SANTOS, JERÓNIMO , Gregory Mertz , Analía Cuiza , Begonia Agüero , Dante Aguilera , Diego Araya , Ignacia Pailamilla , Flavia Paratori , Víctor Torres-Torres , VIAL CLARO, PABLO AGUSTIN , DELGADO BECERRA, OROZIMBA IRIS

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/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.

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Deletions in Genes Participating in Innate Immune Response Modify the Clinical Course of Andes Orthohantavirus Infection

2019 , Grazielle Esteves Ribeiro , Luis Edgardo Leon , Ruth Perez , Analia Cuiza , Pablo Agustin Vial , Marcela Ferres , Gregory J. Mertz , VIAL COX, MARIA 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.