Browsing by Author "Mertz, Gregory J."

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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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    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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    PREDICTING HANTAVIRUS RISK IN CHILE
    (AMER SOC TROP MED & HYGIENE, 2008) Glass, Gregory E.; Marquet Iturriaga Pablo Angel; Palma Troncoso Rodrigo Eduardo; Barria, Ivan; Yates, Terry L.; Vial, Pablo A.; Ferres Garrido, Marcela Viviana; Mertz, Gregory J.