HANTAVIRUS ECOLOGY AND DISEASE IN CHILE AND PANAMA

Summary

Principal Investigator: Gregory Mertz
Abstract: DESCRIPTION (provided by applicant): 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.
Funding Period: 1999-09-15 - 2010-04-30
more information: NIH RePORT

Top Publications

  1. pmc Rapid enzyme-linked immunosorbent assay for the detection of hantavirus-specific antibodies in divergent small mammals
    Karla Cautivo
    Instituto de Biologia, Pontificia Universidad Catolica de Valparaiso, Valparaíso 2373223, Chile
    Viruses 6:2028-37. 2014
  2. pmc Convalescent pulmonary dysfunction following hantavirus pulmonary syndrome in Panama and the United States
    Fernando Gracia
    Ministry of Health, Panama City, Republic of Panama
    Lung 188:387-91. 2010
  3. pmc Highly differentiated, resting gn-specific memory CD8+ T cells persist years after infection by andes hantavirus
    Tobias Manigold
    Institute of Science, Medical School, Clinica Alemana Universidad Del Desarrollo, Santiago, Chile
    PLoS Pathog 6:e1000779. 2010
  4. pmc Kinetics of immune responses in deer mice experimentally infected with Sin Nombre virus
    Tony Schountz
    School of Biological Sciences, University of Northern Colorado, Greeley, Colorado, USA
    J Virol 86:10015-27. 2012
  5. pmc High-dose intravenous methylprednisolone for hantavirus cardiopulmonary syndrome in Chile: a double-blind, randomized controlled clinical trial
    Pablo A Vial
    Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago
    Clin Infect Dis 57:943-51. 2013
  6. pmc Hantavirus fever without pulmonary syndrome in Panama
    Blas Armien
    Epidemiology and Microbiology, Gorgas Memorial Institute for Health Research, Panama City, Panama
    Am J Trop Med Hyg 89:489-94. 2013
  7. ncbi Human hantavirus infections: epidemiology, clinical features, pathogenesis and immunology
    Tobias Manigold
    Internal Medicine, University Hospital, Basel, Switzerland
    Swiss Med Wkly 144:w13937. 2014
  8. ncbi Ecology of rodent-associated hantaviruses in the Southern Cone of South America: Argentina, Chile, Paraguay, and Uruguay
    R Eduardo Palma
    Departamento de Ecología and Centro de Estudios Avanzados en Ecología y Biodiversidad, CASEB, Pontificia Universidad Catolica de Chile, Alameda 340, Santiago 6513677, Chile
    J Wildl Dis 48:267-81. 2012
  9. pmc Incidence rate for hantavirus infections without pulmonary syndrome, Panama
    Blas Armien
    Gorgas Memorial Institute for Health Research, Panama City, Panama
    Emerg Infect Dis 17:1936-9. 2011
  10. pmc Spatial but not temporal co-divergence of a virus and its mammalian host
    Fernando Torres-Pérez
    Instituto de Biologia, Pontificia Universidad Catolica de Valparaiso, Valparaiso, Chile
    Mol Ecol 20:4109-22. 2011

Scientific Experts

  • Brian L Hjelle
  • R Eduardo Palma
  • Lauren Oko
  • Fernando Torres-Pérez
  • Frederick Koster
  • Angel E Spotorno
  • Tobias Manigold
  • A G Armien
  • Pablo A Vial
  • Scott L Gardner
  • Blas Armien
  • Rafael A Medina
  • Marcela Ferres
  • Tony Schountz
  • Carlos Munoz
  • Jonas Schmidt
  • Fernando Gracia
  • Karla Cautivo
  • Mariana Acuna-Retamar
  • Juan M Pascale
  • Indre Kucinskaite-Kodze
  • Candida Broce
  • Randin Nelson
  • Juan Miguel Pascale
  • Chunyan Ye
  • Sang Joon Lee
  • Paula Padula
  • Francisca Valdivieso
  • Detlev H Kruger
  • Helga Meisel
  • Rainer Ulrich
  • Jamileth Mariñas
  • Heydy Núñez
  • JOSE TRUJILLO
  • Deyanira Sánchez
  • Milagro Herrera
  • Yaxelis Mendoza
  • Shira Feinstein
  • Staci Peters
  • Brendan Podell
  • William C Black
  • Joseph Prescott
  • Marc Mertens
  • Kestutis Sasnauskas
  • Kook L Choi
  • Rasa Petraityte-Burneikiene
  • Jonas Schmidt-Chanasit
  • Rainer G Ulrich
  • Mario Avila
  • Aurelija Zvirbliene
  • Alma Gedvilaite
  • Ausra Razanskiene
  • Steven Q Simpson
  • Raul Cañate
  • Jerry W Dragoo
  • Joseph A Cook
  • Maritza Navarrete
  • Hector Galeno
  • Constanza Castillo
  • Gregory J Mertz
  • Claudia Marco
  • Lia Yanez
  • Julie Hutt
  • Paula Godoy
  • Katy Mirowsky-Garcia
  • Iris Delgado
  • Analia Cuiza
  • Diane Goade
  • Rasa Petraityte
  • Ake Lundkvist
  • Silvana G Capria

Detail Information

Publications27

  1. pmc Rapid enzyme-linked immunosorbent assay for the detection of hantavirus-specific antibodies in divergent small mammals
    Karla Cautivo
    Instituto de Biologia, Pontificia Universidad Catolica de Valparaiso, Valparaíso 2373223, Chile
    Viruses 6:2028-37. 2014
    ..This assay can be used for the rapid detection of antibodies to divergent hantaviruses from geographically and phylogenetically distant rodent species. ..
  2. pmc Convalescent pulmonary dysfunction following hantavirus pulmonary syndrome in Panama and the United States
    Fernando Gracia
    Ministry of Health, Panama City, Republic of Panama
    Lung 188:387-91. 2010
    ..Temporary exertional dyspnea and reduced expiratory flow are common in early convalescence after HPS but resolves in almost all patients...
  3. pmc Highly differentiated, resting gn-specific memory CD8+ T cells persist years after infection by andes hantavirus
    Tobias Manigold
    Institute of Science, Medical School, Clinica Alemana Universidad Del Desarrollo, Santiago, Chile
    PLoS Pathog 6:e1000779. 2010
    ..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...
  4. pmc Kinetics of immune responses in deer mice experimentally infected with Sin Nombre virus
    Tony Schountz
    School of Biological Sciences, University of Northern Colorado, Greeley, Colorado, USA
    J Virol 86:10015-27. 2012
    ..Together, these data suggest that a subtle immune response that fails to clear the virus occurs in deer mice...
  5. pmc High-dose intravenous methylprednisolone for hantavirus cardiopulmonary syndrome in Chile: a double-blind, randomized controlled clinical trial
    Pablo A Vial
    Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago
    Clin Infect Dis 57:943-51. 2013
    ..In an immunomodulatory approach, we evaluated the efficacy of intravenous methylprednisolone for HCPS treatment, through a parallel-group, placebo-controlled clinical trial...
  6. pmc Hantavirus fever without pulmonary syndrome in Panama
    Blas Armien
    Epidemiology and Microbiology, Gorgas Memorial Institute for Health Research, Panama City, Panama
    Am J Trop Med Hyg 89:489-94. 2013
    ..HV infection caused by Choclo virus in Panama presents often as HF, which contrasts with HV in the Americas but is consistent with the high seroprevalence in endemic regions...
  7. ncbi Human hantavirus infections: epidemiology, clinical features, pathogenesis and immunology
    Tobias Manigold
    Internal Medicine, University Hospital, Basel, Switzerland
    Swiss Med Wkly 144:w13937. 2014
    ..This review summarises clinical features and current epidemiological findings, as well as concepts regarding the immunology, pathogenesis and intervention strategies of human hantaviral diseases. ..
  8. ncbi Ecology of rodent-associated hantaviruses in the Southern Cone of South America: Argentina, Chile, Paraguay, and Uruguay
    R Eduardo Palma
    Departamento de Ecología and Centro de Estudios Avanzados en Ecología y Biodiversidad, CASEB, Pontificia Universidad Catolica de Chile, Alameda 340, Santiago 6513677, Chile
    J Wildl Dis 48:267-81. 2012
    ..Ongoing studies are improving our understanding of hantavirus-host ecology and providing tools that may predict human risk...
  9. pmc Incidence rate for hantavirus infections without pulmonary syndrome, Panama
    Blas Armien
    Gorgas Memorial Institute for Health Research, Panama City, Panama
    Emerg Infect Dis 17:1936-9. 2011
    ..Among 1,129 persons, antibody prevalence was 16.5%-60.4%. Repeat surveys of 476 found that patients who seroconverted outnumbered patients with hantavirus pulmonary syndrome by 14 to 1...
  10. pmc Spatial but not temporal co-divergence of a virus and its mammalian host
    Fernando Torres-Pérez
    Instituto de Biologia, Pontificia Universidad Catolica de Valparaiso, Valparaiso, Chile
    Mol Ecol 20:4109-22. 2011
    ..However, despite these major differences in evolutionary dynamics, the geographic structure of host and virus converged across large spatial scales...
  11. ncbi Characterization of monoclonal antibodies against hantavirus nucleocapsid protein and their use for immunohistochemistry on rodent and human samples
    Indre Kucinskaite-Kodze
    Institute of Biotechnology, Vilnius University, V Graiciuno 8, 02241 Vilnius, Lithuania
    Arch Virol 156:443-56. 2011
    ..Therefore, the described mAbs represent useful tools for the immunodetection of hantavirus infection...
  12. pmc Confirmation of Choclo virus as the cause of hantavirus cardiopulmonary syndrome and high serum antibody prevalence in Panama
    Randin Nelson
    Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico
    J Med Virol 82:1586-93. 2010
    ....
  13. pmc Glaciation effects on the phylogeographic structure of Oligoryzomys longicaudatus (Rodentia: Sigmodontinae) in the southern Andes
    R Eduardo Palma
    Centro de Estudios Avanzados en Ecología y Biodiversidad, CASEB, and Departamento de Ecología, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Chile
    PLoS ONE 7:e32206. 2012
    ..From these refugia, O. longicaudatus experienced demographic expansions into Patagonian Forests and central Mediterranean Chile using glacial retreats...
  14. pmc Sin Nombre virus infection in field workers, Colorado, USA
    Fernando Torres-Pérez
    Department of Pathology, University of New Mexico, Albuquerque, New Mexico 87131, USA
    Emerg Infect Dis 16:308-10. 2010
    ..Screening for antibodies to SNV in rodents trapped in 2 seasons showed that 9.77% were seropositive. Quantitative real-time PCR showed that 2 of 79 deer mice had detectable titers of SNV RNA...
  15. pmc Andes virus infections in the rodent reservoir and in humans vary across contrasting landscapes in Chile
    Fernando Torres-Pérez
    Biology Department and Museum of Southwestern Biology, University of New Mexico, Albuquerque, NM 87131, USA
    Infect Genet Evol 10:820-25. 2010
    ..We relate these results to the number of reported human HCPS cases in Chile, and discuss the importance of landscape differences in light of ANDV transmission to humans and among rodent populations...
  16. ncbi Development and evaluation of serological assays for detection of human hantavirus infections caused by Sin Nombre virus
    Jonas Schmidt
    Institute of Virology, Charite School of Medicine, D 10098 Berlin, Germany
    J Clin Virol 33:247-53. 2005
    ..The major causative agent of HCPS in North America is the Sin Nombre virus (SNV) carried by the deer mouse Peromyscus maniculatus. The first HCPS case imported to Europe was reported in 2002...
  17. ncbi Low seroprevalence among farmers from Nebraska and vicinity suggests low level of human exposure to sin nombre virus
    Scott L Gardner
    Harold W Manter Laboratory of Parasitology, School of Biological Sciences, University of Nebraska Lincoln, NE 68588 0514, USA
    J Agromedicine 10:59-61. 2005
  18. ncbi Serological assays for the detection of human andes hantavirus infections based on its yeast-expressed nucleocapsid protein
    Jonas Schmidt
    Institute of Virology, Charite School of Medicine, Berlin, Germany
    Intervirology 49:173-84. 2006
    ....
  19. pmc Neutralizing antibodies in survivors of Sin Nombre and Andes hantavirus infection
    Francisca Valdivieso
    Universidad del Desarrollo, Santiago, Chile
    Emerg Infect Dis 12:166-8. 2006
    ..All but 1 patient had high titers of NAb. None of the plasma samples showed high titers against the heterologous virus...
  20. pmc Profiling helper T cell subset gene expression in deer mice
    Lauren Oko
    School of Biological Sciences, University of Northern Colorado, 1556 Ross Hall, Greeley, CO 80639, USA
    BMC Immunol 7:18. 2006
    ..A neutralizing IgG antibody response occurs, but the virus establishes a persistent infection. Limitations of detailed analysis of deer mouse immune responses to SNV are the lack of reagents and methods for evaluating such responses...
  21. pmc Incubation period of hantavirus cardiopulmonary syndrome
    Pablo A Vial
    Faculdad se Medicina Clinica Alemana, Universidad del Desarrollo, Las Condes 12438, Lo Barnechea, Santiago 0000, Chile
    Emerg Infect Dis 12:1271-3. 2006
    ..This period was 14-32 days (median 18 days) in 11 patients with exposure for <48 hours...
  22. ncbi Ribavirin, human convalescent plasma and anti-beta3 integrin antibody inhibit infection by Sin Nombre virus in the deer mouse model
    Rafael A Medina
    Center for Infectious Diseases and Immunity, Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA
    J Gen Virol 88:493-505. 2007
    ..These results show that ReoPro can lower viral loads and that ribavirin and HIP, but not anti-N antibody, inhibit seroconversion and reduce viral loads in a dose-dependent manner...
  23. ncbi Prospective evaluation of household contacts of persons with hantavirus cardiopulmonary syndrome in chile
    Marcela Ferres
    Department of Pediatrics and Virology Laboratory, Pontificia Universidad Catolica, Santiago, Chile
    J Infect Dis 195:1563-71. 2007
    ..Andes virus (ANDV) infection, which has a case fatality rate of 37% in Chile, often occurs in household clusters and may be transmitted from person to person...
  24. ncbi Case report: T-cell responses during clearance of Andes virus from blood cells 2 months after severe hantavirus cardiopulmonary syndrome
    Tobias Manigold
    Facultad de Medicina, Instituto de Ciencias, Clinica Alemana Universidad Del Desarrollo, Santiago, Chile
    J Med Virol 80:1947-51. 2008
    ..Moreover, the kinetics of T-cell responses during ANDV clearance may indicate a major role of T-cells for clearance of ANDV and human immunity to this pathogen...
  25. pmc Ecology, genetic diversity, and phylogeographic structure of andes virus in humans and rodents in Chile
    Rafael A Medina
    Center for Infectious Diseases and Immunity, Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, USA
    J Virol 83:2446-59. 2009
    ..longicaudatus as the primary ANDV Sout reservoir in Chile. While evidence of geographic differentiation exists, a single cosmopolitan lineage of ANDV Sout remains the sole etiologic agent for HCPS in Chile...
  26. ncbi Hantavirus infection and habitat associations among rodent populations in agroecosystems of Panama: implications for human disease risk
    Anibal G Armien
    Department of Population Medicine, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota 55108, USA
    Am J Trop Med Hyg 81:59-66. 2009
    ..Thus, crop habitats may serve as refugia for invasion into adjacent human residences and suggests several interventions to reduce human infection...
  27. ncbi [Evolutionary medicine: an emergent basic science]
    Angel E Spotorno
    Laboratorio de Genómica Evolutiva, Programa de Genética Humana, Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Chile
    Rev Med Chil 133:231-40. 2005
    ..With the evolutionary approach, post-modern medicine is detecting better the vulnerabilities, restrictions, biases, adaptations and maladaptations of human body, its actual diseases, and its preventions...