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

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          Abstract

          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.

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          Most cited references25

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          Hantavirus pulmonary syndrome: a clinical description of 17 patients with a newly recognized disease. The Hantavirus Study Group.

          In May 1993 an outbreak of severe respiratory illness occurred in the southwestern United States. A previously unknown hantavirus was identified as the cause. In Asia hantaviruses are associated with hemorrhagic fever and renal disease. They have not been known as a cause of human disease in North America. We analyzed clinical, laboratory, and autopsy data on the first 17 persons with confirmed infection from this newly recognized strain of hantavirus. The mean age of the patients was 32.2 years (range, 13 to 64); 61 percent were women, 72 percent were Native American, 22 percent white, and 6 percent Hispanic. The most common prodromal symptoms were fever and myalgia (100 percent), cough or dyspnea (76 percent), gastrointestinal symptoms (76 percent), and headache (71 percent). The most common physical findings were tachypnea (100 percent), tachycardia (94 percent), and hypotension (50 percent). The laboratory findings included leukocytosis (median peak cell count, 26,000 per cubic millimeter), often with myeloid precursors, an increased hematocrit, thrombocytopenia (median lowest platelet count, 64,000 per cubic millimeter), prolonged prothrombin and partial-thromboplastin times, an elevated serum lactate dehydrogenase concentration, decreased serum protein concentrations, and proteinuria. Rapidly progressive acute pulmonary edema developed in 15 of the 17 patients (88 percent), and 13 patients, all of whom had profound hypotension, died (case fatality rate, 76 percent). Increases in the hematocrit and partial-thromboplastin time were predictive of death. Infection with a newly described hantavirus causes the hantavirus pulmonary syndrome, which is characterized by a brief prodromal illness followed by rapidly progressive, noncardiogenic pulmonary edema.
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            Hantavirus pulmonary syndrome outbreak in Argentina: molecular evidence for person-to-person transmission of Andes virus.

            An increase of Hantavirus Pulmonary Syndrome (HPS) cases around a southwestern Argentina town and in persons living 1400 km away but in contact with those cases was detected during the spring of 1996. In order to evaluate person-to-person transmission we compared the homology of PCR-amplified viral sequences of 26 Argentine and Chilean cases. Sixteen of them were epidemiologically linked cases and had the same sequence (Epilink/96) in the S segment 3' noncoding region and in the M segment partial G1 and G2 region (a total of 1075 nucleotides). Contrarily, two geographical and contemporary but nonepidemiologically related cases differed from Epilink/96 in the compared regions. No significant differences, such as glycosylation or hydrophilic pattern, were found between Epilink/96 and the other sequences. Nucleotide and deduced amino acid sequence homologies between samples from southern Argentina and Chile ranged from 90.9 to 100% and 96.4 to 100%, respectively. Phylogenetic analysis revealed that all the analyzed southwestern viruses belong to the Andes lineage. Although human infection principally occurs via inhalation of contaminated rodent excreta, our results with Andes virus show the first direct genetic evidence of person-to-person transmission of a hantavirus.
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              Hantavirus regulation of endothelial cell functions.

              Hantaviruses cause two vascular permeability-based diseases and primarily infect endothelial cells which form the primary fluid barrier of the vasculature. Since hantavirus infections are not lytic, the mechanisms by which hantaviruses cause haemorrhagic fever with renal syndrome (HFRS) or Hantavirus Pulmonary Syndrome (HPS) are indeterminate. HPS is associated with acute pulmonary oedema and HFRS with moderate haemorrhage and renal sequelae, perhaps reflecting the location of vast microvascular beds and endothelial cell reservoirs available for hantavirus infection. Endothelial cells regulate capillary integrity, and hantavirus infection provides a primary means for altering vascular permeability that contributes to pathogenesis. The central importance of endothelial cells in regulating oedema, vascular repair, angiogenesis, immune cell recruitment, platelet deposition as well as gas exchange and solute delivery suggest that a multitude of inputs and cellular responses may be influenced by hantavirus infection and contribute to pathogenic changes in vascular permeability. Here we focus on understanding hantavirus interactions with endothelial cells which are linked to vascular permeability, and provide insight into the contribution of endothelial cell responses in hantavirus pathogenesis.
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                Author and article information

                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                30 July 2019
                August 2019
                : 11
                : 8
                : 693
                Affiliations
                [1 ]Departamento de Paciente Crítico, Clínica Alemana de Santiago, Santiago 7650567, Chile
                [2 ]Escuela de Medicina. Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago 7710162, Chile
                [3 ]Programa Hantavirus, Instituto de Ciencias e Innovación en Medicina (ICIM), Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago 7590943, Chile
                [4 ]Instituto de Medicina, Universidad Austral de Chile, Valdivia 5110566, Chile
                [5 ]Departamento Enfermedades Infecciosas e Inmunología Pediátrica, Laboratorio Infectología y Virología Molecular, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 8331500, Chile
                [6 ]University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
                [7 ]Departamento de Pediatría, Clínica Alemana de Santiago, Santiago 7650567, Chile
                Author notes
                [* ]Correspondence: pvial@ 123456udd.cl
                Author information
                https://orcid.org/0000-0003-4026-6367
                https://orcid.org/0000-0002-0399-6144
                https://orcid.org/0000-0001-5657-7616
                Article
                viruses-11-00693
                10.3390/v11080693
                6724000
                31366116
                c14cb588-0c40-4118-8720-ba8de6b0800a
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 01 June 2019
                : 19 July 2019
                Categories
                Article

                Microbiology & Virology
                hantavirus cardiopulmonary syndrome,hantavirus pulmonary syndrome,thrombocytopenia

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