Hantaviruses are NIH category A pathogens, including the viruses that cause hantavirus cardiopulmonary syndrome (HCPS) in North, Central and South America. Reported cases and deaths from HCPS in Chile (384) and Argentina (595), despite much smaller populations, outnumber cases reported in the United States (379), and case fatality rates remain at 36-38% in North and South America. There is no known effective treatment or vaccine. In Project 1, Ecology of Andes and Choclo Viruses, we will study the ecology of the rodent reservoirs in Chile and Panama to develop predictive models and rapid interpretation of results from remote monitoring to guide public health intervention. In Project 2, Treatment and Prevention of HCPS, we will complete a controlled trial of intravenous methylprednisolone in persons with suspected HCPS in the cardiopulmonary phase, continue collection of plasma by plasmapheresis of survivors of Andes virus infection and perform three clinical trials with immune plasma with high titers of Andes virus neutralizing activity (HIP). The first trial with HIP will be a phase I, dose-escalation safety and pharmacokinetics trial in a) normal adults and b) persons with HCPS. The second trial will be an open safety and efficacy trial of HIP in persons at high risk of developing HCPS (sex partners of index patients with HCPS who have a 20% risk of developing HCPS). The third trial will be a controlled trial of HIP in persons with suspected HCPS in the cardiopulmonary phase. In Project 3, we will refine our studies to try to learn what factors put sex partners at significantly higher risk of infection than nonsex partner household contacts. We will a) prospectively follow sex partner household contacts, b) administer questionnaires to assess risks such as common source exposure, sexual practices and deep kissing and c) study genital, oral and dermal secretions, including daily home collection of saliva swabs, to determine whether Andes virus RNA can be identified by PCR and whether virus can be cultured from PCR-positive samples. PROJECT 1: Ecology of Andes & Choclo Viruses (Glass, G.) PROJECT 1 DESCRIPTION (provided by applicant): Hantavirus cardiopulmonary syndrome resulting from any of a number of hantaviruses in the western hemisphere is thought to be contracted through inhalation of infected rodent excreta. In southern and central Chile, the Andes virus infects the sigmodontine rodent Oligoryzomys longicaudatus, and causes a rare but severe human infection with high mortality. In western Panama, the Choclo virus infects the rodent Oligoryzomys fulvescens and causes a common but usually mild or inapparent human infection with a low mortality rate. In both regions the risk of transmission appears to be influenced by many factors increasing the opportunity for close contact between infected rodents and susceptible humans. We will focus our investigations on three of these factors, with the goal of gaining insights critical for the design of future environmental interventions to decrease hantavirus transmission. First, recent investigations in Chile and Panama have associated risk of infection with selected vegetation habitats favored by the infected vector rodents. In Chile exposure risk can be predicted by remote sensing with satellite imagery analysis over 2/3 of the country. In Panama a micro scale analysis has suggested complex relationships between peridomestic infected rodents and agricultural activities. We propose to focus on spatial relationships between rodents and habitats over time, using mark-recapture trapping and radiotelemetry to mark rodent movements, particularly in peridomestic environments. Second we will create a dynamic model that extends our current static analysis of risk. The new model will apply graph theory to field collected data of rodent habitat preferences and movements within the landscape to predict the likely movement of infected rodents. We will test the model using data from sites different from those used to create the model. The temporal precision of the model will be improved by quantitating viral load in rodent blood, tissue, and urine in the winter (low transmission) and spring (high transmission) seasons. Finally, serial serosurveys of at-risk human populations in Panama will quantify the impact on human infection associated with spatial-temporal variations in rodent density and movement.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1)
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University of New Mexico
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Armién, Blas; Ortiz, Paulo Lazaro; Gonzalez, Publio et al. (2016) Spatial-Temporal Distribution of Hantavirus Rodent-Borne Infection by Oligoryzomys fulvescens in the Agua Buena Region--Panama. PLoS Negl Trop Dis 10:e0004460
Gutiérrez-Tapia, Pablo; Palma, R Eduardo (2016) Integrating phylogeography and species distribution models: cryptic distributional responses to past climate change in an endemic rodent from the central Chile hotspot. Divers Distrib 22:638-650
Vial, Cecilia; Martinez-Valdebenito, Constanza; Rios, Susana et al. (2016) Molecular method for the detection of Andes hantavirus infection: validation for clinical diagnostics. Diagn Microbiol Infect Dis 84:36-39
Vial, Pablo A; Valdivieso, Francisca; Calvo, Mario et al. (2015) A non-randomized multicentre trial of human immune plasma for treatment of hantavirus cardiopulmonary syndrome caused by Andes virus. Antivir Ther 20:377-86
Campbell, Corey L; Torres-Perez, Fernando; Acuna-Retamar, Mariana et al. (2015) Transcriptome markers of viral persistence in naturally-infected andes virus (bunyaviridae) seropositive long-tailed pygmy rice rats. PLoS One 10:e0122935
Cautivo, Karla; Schountz, Tony; Acuña-Retamar, Mariana et al. (2014) Rapid enzyme-linked immunosorbent assay for the detection of hantavirus-specific antibodies in divergent small mammals. Viruses 6:2028-37
Manigold, Tobias; Vial, Pablo (2014) Human hantavirus infections: epidemiology, clinical features, pathogenesis and immunology. Swiss Med Wkly 144:w13937
Vial, Pablo A; Valdivieso, Francisca; Ferres, Marcela et al. (2013) High-dose intravenous methylprednisolone for hantavirus cardiopulmonary syndrome in Chile: a double-blind, randomized controlled clinical trial. Clin Infect Dis 57:943-51
Armien, Blas; Pascale, Juan M; Muñoz, Carlos et al. (2013) Hantavirus fever without pulmonary syndrome in Panama. Am J Trop Med Hyg 89:489-94
Schountz, Tony; Acuña-Retamar, Mariana; Feinstein, Shira et al. (2012) Kinetics of immune responses in deer mice experimentally infected with Sin Nombre virus. J Virol 86:10015-27

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