Hantavirus pulmonary syndrome, central plateau, southeastern, and southern Brazil.

PubMed

Figueiredo, Luiz T M; Moreli, Marcos L; de-Sousa, Ricardo L M; Borges, Alessandra A; de-Figueiredo, Glauciane G; Machado, Alex M; Bisordi, Ivani; Nagasse-Sugahara, Teresa K; Suzuki, Akemi; Pereira, Luiz E; de-Souza, Renato P; de-Souza, Luiza T M; Braconi, Carla T; Harsi, Charlotte M; de-Andrade-Zanotto, Paolo M

2009-04-01

Hantavirus pulmonary syndrome (HPS) is an increasing health problem in Brazil because of encroachment of sprawling urban, agricultural, and cattle-raising areas into habitats of subfamily Sigmodontinae rodents, which serve as hantavirus reservoirs. From 1993 through June 2007, a total of 884 cases of HPS were reported in Brazil (case-fatality rate 39%). To better understand this emerging disease, we collected 89 human serum samples and 68 rodent lung samples containing antibodies to hantavirus from a 2,500-km-wide area in Brazil. RNA was isolated from human samples and rodent tissues and subjected to reverse transcription-PCR. Partial sequences of nucleocapsid protein and glycoprotein genes from 22 human and 16 rodent sources indicated only Araraquara virus and Juquitiba virus lineages. The case-fatality rate of HPS was higher in the area with Araraquara virus. This virus, which may be the most virulent hantavirus in Brazil, was associated with areas that have had greater anthropogenic changes.

Hantavirus pulmonary syndrome outbreak, Brazil, December 2009-January 2010.

PubMed

Terças, Ana Cláudia Pereira; Atanaka dos Santos, Marina; Pignatti, Marta Gislene; Espinosa, Mariano Martinez; Via, Alba Valéria Gomes de Melo; Menegatti, Jaqueline Aparecida

2013-11-01

An outbreak of hantavirus pulmonary syndrome occurred in the Sobradinho Indian settlement of the Kayabí ethnic group in northern Mato Grosso during December 2009-January 2010. We conducted a retrospective study to clarify the outbreak's epidemiologic and clinical characteristics. Results suggest a relationship between the outbreak and deforestation and farming expansion in indigenous areas.

[Hantavirus pulmonary syndrome in Buenos Aires, 2009-2014].

PubMed

Iglesias, Ayelén A; Bellomo, Carla M; Martínez, Valeria P

2016-01-01

Andes virus is the causative agent of hantavirus pulmonary syndrome (HPS) in Argentina and neighboring countries. In our country four different areas are affected: Northwest, Southwest, Central and Northeast, where distinct Andes virus genotypes were characterized. Three genotypes were described in Buenos Aires province (Central area): AND-Buenos Aires, AND-Lechiguanas and AND-Plata. In this work, we considered all HPS cases confirmed by ELISA and real time RT-PCR during the period 2009-2014 in Buenos Aires province. The annual distribution, fatality rate and geographic distribution were analyzed. We also analyzed the genotypes involved by RT-PCR and nucleotide sequencing. Finally we evaluated epidemiological data in order to establish the route of transmission. We analyzed 1386 suspect cases of hantavirus infection from Buenos Aires province and we confirmed 88 cases of Hantavirus Pulmonary Syndrome during 2009-2014. The overall average was 14.3 cases per year. The occurrence of a HPS outbreak was confirmed in Buenos Aires province during 2013, showing a 3 fold increase in case number compared to the annual average between 2009 and 2012, tending to normalize during 2014. The overall lethality was 25.6%, with a maximum value of 45.5% in 2011. Genotype analysis was performed in 30.7% of confirmed cases, AND-BsAs show the highest incidence, it was characterized in 72% of the studied cases. Epidemiological data and results of viral genome comparison strongly suggest person-to-person transmission in the three clusters of two cases described in our study.

Hantavirus Pulmonary Syndrome in Santa Cruz, Bolivia: Outbreak Investigation and Antibody Prevalence Study

PubMed Central

Montgomery, Joel M.; Blair, Patrick J.; Carroll, Darin S.; Mills, James N.; Gianella, Alberto; Iihoshi, Naomi; Briggiler, Ana M.; Felices, Vidal; Salazar, Milagros; Olson, James G.; Glabman, Raisa A.; Bausch, Daniel G.

2012-01-01

We report the results of an investigation of a small outbreak of hantavirus pulmonary syndrome in 2002 in the Department of Santa Cruz, Bolivia, where the disease had not previously been reported. Two cases were initially reported. The first case was a physician infected with Laguna Negra virus during a weekend visit to his ranch. Four other persons living on the ranch were IgM antibody-positive, two of whom were symptomatic for mild hantavirus pulmonary syndrome. The second case was a migrant sugarcane worker. Although no sample remained to determine the specific infecting hantavirus, a virus 90% homologous with Río Mamoré virus was previously found in small-eared pygmy rice rats (Oligoryzomys microtis) trapped in the area. An antibody prevalence study conducted in the region as part of the outbreak investigation showed 45 (9.1%) of 494 persons to be IgG positive, illustrating that hantavirus infection is common in Santa Cruz Department. Precipitation in the months preceding the outbreak was particularly heavy in comparison to other years, suggesting a possible climatic or ecological influence on rodent populations and risk of hantavirus transmission to humans. Hantavirus infection appears to be common in the Santa Cruz Department, but more comprehensive surveillance and field studies are needed to fully understand the epidemiology and risk to humans. PMID:23094116

[Hantavirus pulmonary syndrome (Rio Mamore virus) in the Peruvian Amazon region].

PubMed

Casapía, Martín; Mamani, Enrique; García, María P; Miraval, María L; Valencia, Pedro; Quino, Alberto H; Alvarez, Carlos; Donaires, Luis F

2012-01-01

Hantavirus infection is a viral zoonotic infection borne by rodents which most letal form clinical is the Hantavirus Pulmonary Syndrome (SPH, Spanish abbreviation). The Mamore River variant originates in South America and was found in rodents without any association to human diseases. Two cases of SPH were identified in the Peruvian Amazon region in November 2011. In both cases, a molecular diagnostic testing was conducted by the Instituto Nacional de Salud from Peru. A phylogenetic analysis of a viral genome fragment and a histopathological evaluation were conducted. Both patients developed adult respiratory distress syndrome and refractory shock. A patient died and another one recovered 12 days later.

An outbreak of hantavirus pulmonary syndrome, Chile, 1997.

PubMed Central

Toro, J.; Vega, J. D.; Khan, A. S.; Mills, J. N.; Padula, P.; Terry, W.; Yadón, Z.; Valderrama, R.; Ellis, B. A.; Pavletic, C.; Cerda, R.; Zaki, S.; Shieh, W. J.; Meyer, R.; Tapia, M.; Mansilla, C.; Baro, M.; Vergara, J. A.; Concha, M.; Calderon, G.; Enria, D.; Peters, C. J.; Ksiazek, T. G.

1998-01-01

An outbreak of 25 cases of Andes virus-associated hantavirus pulmonary syndrome (HPS) was recognized in southern Chile from July 1997 through January 1998. In addition to the HPS patients, three persons with mild hantaviral disease and one person with asymptomatic acute infection were identified. Epidemiologic studies suggested person-to-person transmission in two of three family clusters. Ecologic studies showed very high densities of several species of sigmodontine rodents in the area. PMID:9866751

Pathophysiology of hantavirus pulmonary syndrome in rhesus macaques.

PubMed

Safronetz, David; Prescott, Joseph; Feldmann, Friederike; Haddock, Elaine; Rosenke, Rebecca; Okumura, Atsushi; Brining, Douglas; Dahlstrom, Eric; Porcella, Stephen F; Ebihara, Hideki; Scott, Dana P; Hjelle, Brian; Feldmann, Heinz

2014-05-13

The pathophysiology of hantavirus pulmonary syndrome (HPS) remains unclear because of a lack of surrogate disease models with which to perform pathogenesis studies. Nonhuman primates (NHP) are considered the gold standard model for studying the underlying immune activation/suppression associated with immunopathogenic viruses such as hantaviruses; however, to date an NHP model for HPS has not been described. Here we show that rhesus macaques infected with Sin Nombre virus (SNV), the primary etiological agent of HPS in North America, propagated in deer mice develop HPS, which is characterized by thrombocytopenia, leukocytosis, and rapid onset of respiratory distress caused by severe interstitial pneumonia. Despite establishing a systemic infection, SNV differentially activated host responses exclusively in the pulmonary endothelium, potentially the mechanism leading to acute severe respiratory distress. This study presents a unique chronological characterization of SNV infection and provides mechanistic data into the pathophysiology of HPS in a closely related surrogate animal model. We anticipate this model will advance our understanding of HPS pathogenesis and will greatly facilitate research toward the development of effective therapeutics and vaccines against hantaviral diseases.

Phylogenetic characterization of hantaviruses from wild rodents and hantavirus pulmonary syndrome cases in the state of Parana (southern Brazil).

PubMed

Raboni, Sonia Mara; Hoffmann, Federico G; Oliveira, Renata C; Teixeira, Bernardo R; Bonvicino, Cibele R; Stella, Vanessa; Carstensen, Suzana; Bordignon, Juliano; D'Andrea, Paulo S; Lemos, Elba R S; Duarte Dos Santos, Claudia Nunes

2009-09-01

Over 1,100 cases of hantavirus pulmonary syndrome (HPS) have occurred in Brazil since 1993, but little is known about Brazilian hantaviruses, and many of their rodent hosts remain unknown. The Araucaria hantavirus (ARAUV) was described recently from HPS patients from Paraná, in southern Brazil, but its host could not be identified. In this study, rodents were captured from regions with high HPS prevalence to address this issue. ARAUV RNA was detected in three distantly related rodent species: Oligoryzomys nigripes, Oxymycterus judex and Akodon montensis. Furthermore, a specimen of A. montensis was infected with a Jaborá-like virus, implying that A. montensis can be infected by at least two different hantaviruses. The presence of the same hantavirus strain in three different rodent species and the co-circulation of two different strains in the same rodent species highlight the potential for genomic reassortment, which could have an impact on hantavirus transmission dynamics in nature and on human epidemiology.

Massive plasmablast response elicited in the acute phase of hantavirus pulmonary syndrome.

PubMed

García, Marina; Iglesias, Ayelén; Landoni, Verónica I; Bellomo, Carla; Bruno, Agostina; Córdoba, María Teresa; Balboa, Luciana; Fernández, Gabriela C; Sasiain, María Del Carmen; Martínez, Valeria P; Schierloh, Pablo

2017-05-01

Beside its key diagnostic value, the humoral immune response is thought to play a protective role in hantavirus pulmonary syndrome. However, little is known about the cell source of these antibodies during ongoing human infection. Herein we characterized B-cell subsets circulating in Andes-virus-infected patients. A notable potent plasmablast (PB) response that increased 100-fold over the baseline levels was observed around 1 week after the onset of symptoms. These PB present a CD3 neg CD19 low CD20 neg CD38 hi CD27 hi CD138 +/- IgA +/- surface phenotype together with the presence of cytoplasmic functional immunoglobulins. They are large lymphocytes (lymphoblasts) morphologically coincident with the 'immunoblast-like' cells that have been previously described during blood cytology examinations of hantavirus-infected patients. Immunoreactivity analysis of white blood cell lysates suggests that some circulating PB are virus-specific but we also observed a significant increase of reactivity against virus-unrelated antigens, which suggests a possible bystander effect by polyclonal B-cell activation. The presence of this large and transient PB response raises the question as to whether these cells might have a protective or pathological role during the ongoing hantavirus pulmonary syndrome and suggest their practical application as a diagnostic/prognostic biomarker. © 2017 John Wiley & Sons Ltd.

Hantavirus Pulmonary Syndrome Caused by Maripa Virus in French Guiana, 2008-2016.

PubMed

Matheus, Séverine; Kallel, Hatem; Mayence, Claire; Bremand, Laetitia; Houcke, Stéphanie; Rousset, Dominique; Lacoste, Vincent; de Thoisy, Benoit; Hommel, Didier; Lavergne, Anne

2017-10-01

We report 5 human cases of hantavirus pulmonary syndrome found during surveillance in French Guiana in 2008-2016; of the 5 patients, 4 died. This pathogen should continue to be monitored in humans and rodents in effort to reduce the occurrence of these lethal infections in humans stemming from ecosystem disturbances.

Effect of Vandetanib on Andes virus survival in the hamster model of Hantavirus pulmonary syndrome.

PubMed

Bird, Brian H; Shrivastava-Ranjan, Punya; Dodd, Kimberly A; Erickson, Bobbie R; Spiropoulou, Christina F

2016-08-01

Hantavirus pulmonary syndrome (HPS) is a severe disease caused by hantavirus infection of pulmonary microvascular endothelial cells leading to microvascular leakage, pulmonary edema, pleural effusion and high case fatality. Previously, we demonstrated that Andes virus (ANDV) infection caused up-regulation of vascular endothelial growth factor (VEGF) and concomitant downregulation of the cellular adhesion molecule VE-cadherin leading to increased permeability. Analyses of human HPS-patient sera have further demonstrated increased circulating levels of VEGF. Here we investigate the impact of a small molecule antagonist of the VEGF receptor 2 (VEGFR-2) activation in vitro, and overall impact on survival in the Syrian hamster model of HPS. Copyright © 2016. Published by Elsevier B.V.

Yellow Pygmy Rice Rat (Oligoryzomys flavescens) and Hantavirus Pulmonary Syndrome in Uruguay

PubMed Central

Delfraro, Adriana; Clara, Mario; Tomé, Lorena; Achaval, Federico; Levis, Silvana; Calderón, Gladys; Enria, Delia; Lozano, Mario; Russi, José

2003-01-01

During 5,230 trapping nights, 672 small mammals were trapped in the areas where most hantavirus pulmonary syndrome (HPS) cases occur in Uruguay. Yellow pygmy rice rats (Oligoryzomys flavescens) were the only rodents that showed evidence of antibodies to hantavirus, with a seroprevalence of 2.6%. The rodents were trapped in all the explored environments, and most of the seropositive rodents were found in habitats frequented by humans. Nucleotide sequences were obtained from four HPS case-patients and four yellow pygmy rice rats of the M genome segment. Sequence comparison and phylogenetic analysis showed that rodent-borne viruses and viruses from three HPS case-patients form a well-supported clade and share a 96.4% identity with the previously characterized Central Plata hantavirus. These results suggest that yellow pygmy rice rat (O. flavescens) may be the host for Central Plata, a hantavirus associated with HPS in the southern area of Uruguay.[ PMID:12890326

Notes from the field: hantavirus pulmonary syndrome --- Maine, April 2011.

PubMed

2011-06-17

On April 25, 2011, the Maine Center for Disease Control and Prevention was notified of a suspected case of hantavirus pulmonary syndrome (HPS) in a man aged 70 years with no recent out-of-state travel. The Maine resident went to a community hospital in early April with a 5-day history of fatigue, decreased appetite, weakness, chills, myalgias, and progressive shortness of breath. On examination, he was hypoxic and tachypneic. The patient was admitted with laboratory evidence of acute renal insufficiency, leukocytosis and thrombocytopenia, and appearance of diffuse bilateral infiltrates on chest radiograph. Two days later, he was transferred to a tertiary-care facility for management of respiratory failure with hypoxemia and worsening renal insufficiency. The next day, he was intubated and mechanically ventilated. Serum specimens demonstrated high titers of hantavirus reactive immunoglobulin M (1:6,400) and immunoglobulin G (1:1,600) antibodies. Hantavirus RNA was detected in the patient's blood. The patient was discharged to a skilled nursing facility 1 month after admission and is recovering with extensive rehabilitation.

Vaccines for Hantaviruses: Progress and Issues

DTIC Science & Technology

2012-01-01

511ISSN 1476-058410.1586/ERV.12.15www.expert-reviews.com Editorial Hantaviruses , hemorrhagic fever with renal syndrome & hantavirus pulmonary...syndrome The Hantavirus genus of the fam- ily Bunyaviridae comprises more than 20 viruses, including several human patho- gens. Hantaviruses are...issues Expert Rev. Vaccines 11(5), 511–513 (2012) Keywords: hantavirus pulmonary syndrome • hantaviruses • hemorrhagic fever with renal syndrome

Serological diagnosis of hantavirus pulmonary syndrome in a febrile patient in Colombia.

PubMed

Mattar, Salim; Garzon, Denisse; Tadeu, Luis; Faccini-Martínez, Alvaro A; Mills, James N

2014-08-01

Hantavirus pulmonary syndrome (HPS) is an often fatal rodent-borne zoonosis caused by any of at least 20 hantavirus genotypes distributed throughout the Americas. Although HPS has been documented in several bordering countries, it has not been reported in Colombia. Here we report seroconversion to a hantavirus in paired samples from a hospitalized patient with symptoms compatible with HPS from Montería, Córdoba Department, north-western Colombia. Tests for regionally endemic agents including Plasmodium, Leptospira, Salmonella, dengue virus, Brucella, Rickettsia, human immunodeficiency virus and hepatitis viruses were negative. Because the patient was enrolled in a clinical trial for hemorrhagic fevers conducted by the University of Córdoba, serum samples were collected on admission and at discharge. Testing using Sin Nombre virus ELISA showed IgG and IgM seroconversion between samples. The eventual finding of this first clinical case of hantavirus infection in Colombia is consistent with the high prevalence of hantavirus antibodies in humans in the region and the likely exposure of the patient to rodents. The clinical presentation was similar to that found in neighbouring Panama. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Laguna Negra Virus Infection Causes Hantavirus Pulmonary Syndrome in Turkish Hamsters (Mesocricetus brandti).

PubMed

Hardcastle, K; Scott, D; Safronetz, D; Brining, D L; Ebihara, H; Feldmann, H; LaCasse, R A

2016-01-01

Laguna Negra virus (LNV) is a New World hantavirus associated with severe and often fatal cardiopulmonary disease in humans, known as hantavirus pulmonary syndrome (HPS). Five hamster species were evaluated for clinical and serologic responses following inoculation with 4 hantaviruses. Of the 5 hamster species, only Turkish hamsters infected with LNV demonstrated signs consistent with HPS and a fatality rate of 43%. Clinical manifestations in infected animals that succumbed to disease included severe and rapid onset of dyspnea, weight loss, leukopenia, and reduced thrombocyte numbers as compared to uninfected controls. Histopathologic examination revealed lung lesions that resemble the hallmarks of HPS in humans, including interstitial pneumonia and pulmonary edema, as well as generalized infection of endothelial cells and macrophages in major organ tissues. Histologic lesions corresponded to the presence of viral antigen in affected tissues. To date, there have been no small animal models available to study LNV infection and pathogenesis. The Turkish hamster model of LNV infection may be important in the study of LNV-induced HPS pathogenesis and development of disease treatment and prevention strategies. © The Author(s) 2015.

Hantavirus Pulmonary Syndrome Caused by Maripa Virus in French Guiana, 2008–2016

PubMed Central

Kallel, Hatem; Mayence, Claire; Bremand, Laetitia; Houcke, Stéphanie; Rousset, Dominique; Lacoste, Vincent; de Thoisy, Benoit; Hommel, Didier; Lavergne, Anne

2017-01-01

We report 5 human cases of hantavirus pulmonary syndrome found during surveillance in French Guiana in 2008–2016; of the 5 patients, 4 died. This pathogen should continue to be monitored in humans and rodents in effort to reduce the occurrence of these lethal infections in humans stemming from ecosystem disturbances. PMID:28930019

Viral load of patients with hantavirus pulmonary syndrome in Argentina.

PubMed

Bellomo, Carla María; Pires-Marczeski, Fanny Clara; Padula, Paula Julieta

2015-11-01

Hantavirus causes severe illness including pneumonia, which leads to hospitalization and often death. At present, there is no specific treatment available. The hantavirus pathogenesis is not well understood, but most likely both virus-mediated and host-mediated mechanisms, are involved. The aim of this study was to correlate viral load in samples of hantavirus pulmonary syndrome cases and hantavirus infected individuals, with clinical epidemiological parameters and disease outcome. The variables that could potentially be related with viral load were analyzed. The retrospective study included 73 cases or household contacts, with different clinical evolution. Viral load was measured by reverse-transcription and real time polymerase chain reaction. There was no statistically significant association between blood viral RNA levels and severity of disease. However, viral load was inversely correlated with IgG response in a statistically significant manner. The level of viral RNA was significantly higher in patients infected with Andes virus South lineage, and was markedly low in persons infected with Laguna Negra virus. These results suggest that the infecting viral genotype is associated with disease severity, and that high viral load is associated with a low specific IgG response. Sex, age and disease severity were not related with viral load. Further investigations increasing strikingly the number of cases and also limiting the variables to be studied are necessary. © 2015 Wiley Periodicals, Inc.

The Syrian hamster model of hantavirus pulmonary syndrome.

PubMed

Safronetz, David; Ebihara, Hideki; Feldmann, Heinz; Hooper, Jay W

2012-09-01

Hantavirus pulmonary syndrome (HPS) is a relatively rare, but frequently fatal disease associated with New World hantaviruses, most commonly Sin Nombre and Andes viruses in North and South America, respectively. It is characterized by fever and the sudden, rapid onset of severe respiratory distress and cardiogenic shock, which can be fatal in up to 50% of cases. Currently there are no approved antiviral therapies or vaccines for the treatment or prevention of HPS. A major obstacle in the development of effective medical countermeasures against highly pathogenic agents like the hantaviruses is recapitulating the human disease as closely as possible in an appropriate and reliable animal model. To date, the only animal model that resembles HPS in humans is the Syrian hamster model. Following infection with Andes virus, hamsters develop HPS-like disease which faithfully mimics the human condition with respect to incubation period and pathophysiology of disease. Perhaps most importantly, the sudden and rapid onset of severe respiratory distress observed in humans also occurs in hamsters. The last several years has seen an increase in studies utilizing the Andes virus hamster model which have provided unique insight into HPS pathogenesis as well as potential therapeutic and vaccine strategies to treat and prevent HPS. The purpose of this article is to review the current understanding of HPS disease progression in Syrian hamsters and discuss the suitability of utilizing this model to evaluate potential medical countermeasures against HPS. Copyright © 2012 Elsevier B.V. All rights reserved.

The Syrian hamster model of hantavirus pulmonary syndrome

PubMed Central

Safronetz, David; Ebihara, Hideki; Feldmann, Heinz; Hooper, Jay W.

2012-01-01

Hantavirus pulmonary syndrome (HPS) is a relatively rare, but frequently fatal disease associated with New World hantaviruses, most commonly Sin Nombre and Andes viruses in North and South America, respectively. It is characterized by fever and the sudden, rapid onset of severe respiratory distress and cardiogenic shock, which can be fatal in up to 50% of cases. Currently there are no approved antiviral therapies or vaccines for the treatment or prevention of HPS. A major obstacle in the development of effective medical countermeasures against highly pathogenic agents like the hantaviruses is recapitulating the human disease as closely as possible in an appropriate and reliable animal model. To date, the only animal model that resembles HPS in humans is the Syrian hamster model. Following infection with Andes virus, hamsters develop HPS-like disease which faithfully mimics the human condition with respect to incubation period and pathophysiology of disease. Perhaps most importantly, the sudden and rapid onset of severe respiratory distress observed in humans also occurs in hamsters. The last several years has seen an increase in studies utilizing the Andes virus hamster model which have provided unique insight into HPS pathogenesis as well as potential therapeutic and vaccine strategies to treat and prevent HPS. The purpose of this article is to review the current understanding of HPS disease progression in Syrian hamsters and discuss the suitability of utilizing this model to evaluate potential medical countermeasures against HPS. PMID:22705798

Diagnosis of hantavirus infection in humans.

PubMed

Mattar, Salim; Guzmán, Camilo; Figueiredo, Luis Tadeu

2015-08-01

Rodent-borne hantaviruses (family Bunyaviridae, genus Hantavirus) cause hantavirus pulmonary syndrome in the Americas and hemorrhagic fever with renal syndrome in Europe and Asia. The viruses are transmitted to humans mainly by inhalation of virus-contaminated aerosols of rodent excreta and secreta. Classic clinical hemorrhagic fever with renal syndrome occurs in five phases: fever, hypotension, oliguria, polyuria, and convalescence. Hantavirus pulmonary syndrome is a severe acute disease that is associated with respiratory failure, pulmonary edema and cardiogenic shock. The diagnosis of hantavirus infections in humans is based on clinical and epidemiological information as well as laboratory tests. We review diagnosis for hantavirus infections based on serology, PCR, immunochemistry and virus culture.

T cells are not required for pathogenesis in the Syrian hamster model of hantavirus pulmonary syndrome.

PubMed

Hammerbeck, Christopher D; Hooper, Jay W

2011-10-01

Andes virus (ANDV) is associated with a lethal vascular leak syndrome in humans termed hantavirus pulmonary syndrome (HPS). In hamsters, ANDV causes a respiratory distress syndrome closely resembling human HPS. The mechanism for the massive vascular leakage associated with HPS is poorly understood; however, T cell immunopathology has been implicated on the basis of circumstantial and corollary evidence. Here, we show that following ANDV challenge, hamster T cell activation corresponds with the onset of disease. However, treatment with cyclophosphamide or specific T cell depletion does not impact the course of disease or alter the number of surviving animals, despite significant reductions in T cell number. These data demonstrate, for the first time, that T cells are not required for hantavirus pathogenesis in the hamster model of human HPS. Depletion of T cells from Syrian hamsters did not significantly influence early events in disease progression. Moreover, these data argue for a mechanism of hantavirus-induced vascular permeability that does not involve T cell immunopathology.

Hemorrhagic Fever with Renal Syndrome in the New, and Hantavirus Pulmonary Syndrome in the Old World: paradi(se)gm lost or regained?

PubMed

Clement, Jan; Maes, Piet; Van Ranst, Marc

2014-07-17

Since the first clinical description in 1994 of the so-called "Hantavirus Pulmonary Syndrome" (HPS) as a "newly recognized disease", hantavirus infections have always been characterized as presenting in two distinct syndromes, the so-called "Hemorrhagic Fever with Renal Syndrome" (HFRS) in the Old World, with the kidney as main target organ, in contrast to HPS in the New World, with the lung as main target organ. However, European literature mentions already since 1934 a mostly milder local HFRS form, aptly named "nephropathia epidemica" (NE), and caused by the prototype European hantavirus species Puumala virus (PUUV). Several NE reports dating from the 1980s and early 1990s described already non-cardiogenic HPS-like lung involvement, prior to any kidney involvement, and increasing evidence is now mounting that a considerable clinical overlap exists between HPS and HFRS. Moreover, growing immunologic insights point to common pathologic mechanisms, leading to capillary hyperpermeability, the cardinal feature of all hantavirus infections, both of the New and Old World. It is now perhaps time to reconsider the paradigm of two "different" syndromes caused by viruses of the same Hantavirus genus in the same Bunyaviridae family, and to agree on a common, more logical disease denomination, such as simply and briefly "Hantavirus fever". Copyright © 2014 Elsevier B.V. All rights reserved.

Hantavirus pulmonary syndrome in Argentina, 1995-2008.

PubMed

Martinez, Valeria P; Bellomo, Carla M; Cacace, Maria Luisa; Suarez, Paola; Bogni, Liliana; Padula, Paula J

2010-12-01

We report a large case series of hantavirus pulmonary syndrome (HPS) in Argentina that was confirmed by laboratory results from 1995 through 2008. The geographic and temporal distribution of cases by age, sex, fatality rate, and risk factors for HPS was analyzed. A total of 710 cases were unequally distributed among 4 of the 5 Argentine regions. Different case-fatality rates were observed for each affected region, with a maximum rate of 40.5%. The male-to-female ratio for HPS case-patients was 3.7:1.0; the case-fatality rate was significantly higher for women. Agriculture-associated activities were most commonly reported as potential risk factors, especially among men of working age. Although HPS cases occurred predominantly in isolation, we identified 15 clusters in which strong relationships were observed between members, which suggests ongoing but limited person-to-person transmission.

Hantavirus pulmonary syndrome in visitors to a national park--Yosemite Valley, California, 2012.

PubMed

2012-11-23

On August 16, 2012, the California Department of Public Health announced two confirmed cases of hantavirus pulmonary syndrome (HPS) in California residents who had stayed overnight in Yosemite National Park, launching an investigation by the National Park Service, California Department of Public Health, and CDC. On August 27, Yosemite National Park announced two additional cases, and by October 30, 10 cases had been confirmed.

Multiplex Analysis of Serum Cytokines in Humans with Hantavirus Pulmonary Syndrome.

PubMed

Morzunov, Sergey P; Khaiboullina, Svetlana F; St Jeor, Stephen; Rizvanov, Albert A; Lombardi, Vincent C

2015-01-01

Hantavirus pulmonary syndrome (HPS) is an acute zoonotic disease transmitted primarily through inhalation of virus-contaminated aerosols. Hantavirus infection of endothelial cells leads to increased vascular permeability without a visible cytopathic effect. For this reason, it has been suggested that the pathogenesis of HPS is indirect with immune responses, such as cytokine production, playing a dominant role. In order to investigate their potential contribution to HPS pathogenesis, we analyzed the serum of hantavirus-infected subjects and healthy controls for 68 different cytokines, chemokines, angiogenic, and growth factors. Our analysis identified differential expression of cytokines that promote tissue migration of mononuclear cells including T lymphocytes, natural killer cells, and dendritic cells. Additionally, we observed a significant upregulation of cytokines known to regulate leukocyte migration and subsequent repair of lung tissue, as well as cytokines known to increase endothelial monolayer permeability and facilitate leukocyte transendothelial migration. Conversely, we observed a downregulation of cytokines associated with platelet numbers and function, consistent with the thrombocytopenia observed in subjects with HPS. This study corroborates clinical findings and extends our current knowledge regarding immunological and laboratory findings in subjects with HPS.

T Cells Are Not Required for Pathogenesis in the Syrian Hamster Model of Hantavirus Pulmonary Syndrome ▿

PubMed Central

Hammerbeck, Christopher D.; Hooper, Jay W.

2011-01-01

Andes virus (ANDV) is associated with a lethal vascular leak syndrome in humans termed hantavirus pulmonary syndrome (HPS). In hamsters, ANDV causes a respiratory distress syndrome closely resembling human HPS. The mechanism for the massive vascular leakage associated with HPS is poorly understood; however, T cell immunopathology has been implicated on the basis of circumstantial and corollary evidence. Here, we show that following ANDV challenge, hamster T cell activation corresponds with the onset of disease. However, treatment with cyclophosphamide or specific T cell depletion does not impact the course of disease or alter the number of surviving animals, despite significant reductions in T cell number. These data demonstrate, for the first time, that T cells are not required for hantavirus pathogenesis in the hamster model of human HPS. Depletion of T cells from Syrian hamsters did not significantly influence early events in disease progression. Moreover, these data argue for a mechanism of hantavirus-induced vascular permeability that does not involve T cell immunopathology. PMID:21775442

Hantavirus pulmonary syndrome in a highly endemic area of Brazil.

PubMed

Oliveira, R C; Sant'ana, M M; Guterres, A; Fernandes, J; Hillesheim, N L F K; Lucini, C; Gomes, R; Lamas, C; Bochner, R; Zeccer, S; DE Lemos, E R S

2016-04-01

Hantavirus pulmonary syndrome (HPS) is the most frequently reported fatal rodent-borne disease in Brazil, with the majority of cases occurring in Santa Catarina. We analysed the clinical, laboratory and epidemiological data of the 251 confirmed cases of HPS in Santa Catarina in 1999-2011. The number of cases ranged from 10 to 47 per year, with the highest incidences in 2004-2006. Gastrointestinal tract manifestations were found in >60% of the cases, potentially confounding diagnosis and leading to inappropriate therapy. Dyspnoea, acute respiratory failure, renal failure, increased serum creatinine and urea levels, increased haematocrits and the presence of pulmonary interstitial infiltrate were significantly more common in HPS patients who died. In addition, we demonstrated that the six cases from the midwest region of the state were associated with Juquitiba virus genotype. The case-fatality rate in this region, 19·2%, was lower than that recorded for other mesoregions. In the multivariate analysis increase of serum creatinine and urea was associated with death by HPS. Our findings help elucidate the epidemiology of HPS in Brazil, where mast seeding of bamboo can trigger rodent population eruptions and subsequent human HPS outbreaks. We also emphasize the need for molecular confirmation of the hantavirus genotype of human cases for a better understanding of the mortality-related factors associated with HPS cases in Brazil.

Genetic characterization of hantaviruses associated with sigmodontine rodents in an endemic area for hantavirus pulmonary syndrome in southern Brazil.

PubMed

de Oliveira, Renata Carvalho; Padula, Paula J; Gomes, Raphael; Martinez, Valeria P; Bellomo, Carla; Bonvicino, Cibele R; Freire e Lima, Danúbia Inês; Bragagnolo, Camila; Caldas, Antônio C S; D'Andrea, Paulo S; de Lemos, Elba R S

2011-03-01

An ecological assessment of reservoir species was conducted in a rural area (Jaborá) in the mid-west of the state of Santa Catarina in southern Brazil, where hantavirus pulmonary syndrome is endemic, to evaluate the prevalence of hantavirus infection in wild rodents. Blood and tissue samples were collected from 507 rodents during seven field trips from March 2004 to April 2006. Some of the animals were karyotyped to confirm morphological identification. Phylogenetic reconstructions of rodent specimens, based on the mitochondrial DNA cytochrome b gene sequences, were also obtained. Hantavirus antibody was found in 22 (4.3%) of the 507 rodents: 5 Akodon montensis, 2 Akodon paranaensis, 14 Oligoryzomys nigripes, and 1 Sooretamys angouya. Viral RNAs detected in O. nigripes and A. montensis were amplified and sequenced. O. nigripes virus genome was 97.5% (nt) and 98.4% (nt) identical to sequences published for Araucaria (Juquitiba-like) virus based on N and G2 fragment sequences. Viral sequences from A. montensis strain showed 89% and 88% nucleotide identities in a 905-nt fragment of the nucleocapsid (N) protein-coding region of the S segment when it was compared with two other Akodontine rodent-associated viruses from Paraguay, A. montensis and Akodon cursor, respectively. Phylogenetic analysis showed the cocirculation of two genetic hantavirus lineages in the state of Santa Catarina, one from O. nigripes and the other from A. montensis, previously characterized in Brazil and Paraguay, respectively. The hantavirus associated with A. montensis, designed Jaborá virus, represents a distinct phylogenetic lineage among the Brazilian hantaviruses.

Hantavirus pulmonary syndrome, United States, 1993-2009.

PubMed

MacNeil, Adam; Ksiazek, Thomas G; Rollin, Pierre E

2011-07-01

Hantavirus pulmonary syndrome (HPS) is a severe respiratory illness identified in 1993. Since its identification, the Centers for Disease Control and Prevention has obtained standardized information about and maintained a registry of all laboratory-confirmed HPS cases in the United States. During 1993-2009, a total of 510 HPS cases were identified. Case counts have varied from 11 to 48 per year (case-fatality rate 35%). However, there were no trends suggesting increasing or decreasing case counts or fatality rates. Although cases were reported in 30 states, most cases occurred in the western half of the country; annual case counts varied most in the southwestern United States. Increased hematocrits, leukocyte counts, and creatinine levels were more common in HPS case-patients who died. HPS is a severe disease with a high case-fatality rate, and cases continue to occur. The greatest potential for high annual HPS incidence exists in the southwestern United States.

A Lethal Disease Model for Hantavirus Pulmonary Syndrome in Immunosuppressed Syrian Hamsters Infected with Sin Nombre Virus

PubMed Central

Brocato, Rebecca L.; Hammerbeck, Christopher D.; Bell, Todd M.; Wells, Jay B.; Queen, Laurie A.

2014-01-01

Sin Nombre virus (SNV) is a rodent-borne hantavirus that causes hantavirus pulmonary syndrome (HPS) predominantly in North America. SNV infection of immunocompetent hamsters results in an asymptomatic infection; the only lethal disease model for a pathogenic hantavirus is Andes virus (ANDV) infection of Syrian hamsters. Efforts to create a lethal SNV disease model in hamsters by repeatedly passaging virus through the hamster have demonstrated increased dissemination of the virus but no signs of disease. In this study, we demonstrate that immunosuppression of hamsters through the administration of a combination of dexamethasone and cyclophosphamide, followed by infection with SNV, results in a vascular leak syndrome that accurately mimics both HPS disease in humans and ANDV infection of hamsters. Immunosuppressed hamsters infected with SNV have a mean number of days to death of 13 and display clinical signs associated with HPS, including pulmonary edema. Viral antigen was widely detectable throughout the pulmonary endothelium. Histologic analysis of lung sections showed marked inflammation and edema within the alveolar septa of SNV-infected hamsters, results which are similar to what is exhibited by hamsters infected with ANDV. Importantly, SNV-specific neutralizing polyclonal antibody administered 5 days after SNV infection conferred significant protection against disease. This experiment not only demonstrated that the disease was caused by SNV, it also demonstrated the utility of this animal model for testing candidate medical countermeasures. This is the first report of lethal disease caused by SNV in an adult small-animal model. PMID:24198421

A lethal disease model for hantavirus pulmonary syndrome in immunosuppressed Syrian hamsters infected with Sin Nombre virus.

PubMed

Brocato, Rebecca L; Hammerbeck, Christopher D; Bell, Todd M; Wells, Jay B; Queen, Laurie A; Hooper, Jay W

2014-01-01

Sin Nombre virus (SNV) is a rodent-borne hantavirus that causes hantavirus pulmonary syndrome (HPS) predominantly in North America. SNV infection of immunocompetent hamsters results in an asymptomatic infection; the only lethal disease model for a pathogenic hantavirus is Andes virus (ANDV) infection of Syrian hamsters. Efforts to create a lethal SNV disease model in hamsters by repeatedly passaging virus through the hamster have demonstrated increased dissemination of the virus but no signs of disease. In this study, we demonstrate that immunosuppression of hamsters through the administration of a combination of dexamethasone and cyclophosphamide, followed by infection with SNV, results in a vascular leak syndrome that accurately mimics both HPS disease in humans and ANDV infection of hamsters. Immunosuppressed hamsters infected with SNV have a mean number of days to death of 13 and display clinical signs associated with HPS, including pulmonary edema. Viral antigen was widely detectable throughout the pulmonary endothelium. Histologic analysis of lung sections showed marked inflammation and edema within the alveolar septa of SNV-infected hamsters, results which are similar to what is exhibited by hamsters infected with ANDV. Importantly, SNV-specific neutralizing polyclonal antibody administered 5 days after SNV infection conferred significant protection against disease. This experiment not only demonstrated that the disease was caused by SNV, it also demonstrated the utility of this animal model for testing candidate medical countermeasures. This is the first report of lethal disease caused by SNV in an adult small-animal model.

Hantavirus Pulmonary Syndrome in Argentina, 1995–2008

PubMed Central

Bellomo, Carla M.; Cacace, María Luisa; Suárez, Paola; Bogni, Liliana; Padula, Paula J.

2010-01-01

We report a large case series of hantavirus pulmonary syndrome (HPS) in Argentina that was confirmed by laboratory restuls from 1995 through 2008. The geographic and temporal distribution of cases by age, sex, fatality rate, and risk factors for HPS was analyzed. A total of 710 cases were unequally distributed among 4 of the 5 Argentine regions. Different case-fatality rates were observed for each affected region, with a maximum rate of 40.5%. The male-to-female ratio for HPS case-patients was 3.7:1.0; the case-fatality rate was significantly higher for women. Agriculture-associated activities were most commonly reported as potential risk factors, especially among men of working age. Although HPS cases occurred predominantly in isolation, we identified 15 clusters in which strong relationships were observed between members, which suggests ongoing but limited person-to-person transmission. PMID:21122213

Novel camelid antibody fragments targeting recombinant nucleoprotein of Araucaria hantavirus: a prototype for an early diagnosis of Hantavirus Pulmonary Syndrome.

PubMed

Pereira, Soraya S; Moreira-Dill, Leandro S; Morais, Michelle S S; Prado, Nidiane D R; Barros, Marcos L; Koishi, Andrea C; Mazarrotto, Giovanny A C A; Gonçalves, Giselle M; Zuliani, Juliana P; Calderon, Leonardo A; Soares, Andreimar M; Pereira da Silva, Luiz H; Duarte dos Santos, Claudia N; Fernandes, Carla F C; Stabeli, Rodrigo G

2014-01-01

In addition to conventional antibodies, camelids produce immunoglobulins G composed exclusively of heavy chains in which the antigen binding site is formed only by single domains called VHH. Their particular characteristics make VHHs interesting tools for drug-delivery, passive immunotherapy and high-throughput diagnosis. Hantaviruses are rodent-borne viruses of the Bunyaviridae family. Two clinical forms of the infection are known. Hemorrhagic Fever with Renal Syndrome (HFRS) is present in the Old World, while Hantavirus Pulmonary Syndrome (HPS) is found on the American continent. There is no specific treatment for HPS and its diagnosis is carried out by molecular or serological techniques, using mainly monoclonal antibodies or hantavirus nucleoprotein (N) to detect IgM and IgG in patient serum. This study proposes the use of camelid VHHs to develop alternative methods for diagnosing and confirming HPS. Phage display technology was employed to obtain VHHs. After immunizing one Lama glama against the recombinant N protein (prNΔ₈₅) of a Brazilian hantavirus strain, VHH regions were isolated to construct an immune library. VHHs were displayed fused to the M13KO7 phage coat protein III and the selection steps were performed on immobilized prNΔ₈₅. After selection, eighty clones recognized specifically the N protein. These were sequenced, grouped based mainly on the CDRs, and five clones were analyzed by western blot (WB), surface plasmon resonance (SPR) device, and ELISA. Besides the ability to recognize prNΔ85 by WB, all selected clones showed affinity constants in the nanomolar range. Additionaly, the clone KC329705 is able to detect prNΔ₈₅ in solution, as well as the native viral antigen. Findings support the hypothesis that selected VHHs could be a powerful tool in the development of rapid and accurate HPS diagnostic assays, which are essential to provide supportive care to patients and reduce the high mortality rate associated with hantavirus

Novel Camelid Antibody Fragments Targeting Recombinant Nucleoprotein of Araucaria hantavirus: A Prototype for an Early Diagnosis of Hantavirus Pulmonary Syndrome

PubMed Central

Pereira, Soraya S.; Moreira-Dill, Leandro S.; Morais, Michelle S. S.; Prado, Nidiane D. R.; Barros, Marcos L.; Koishi, Andrea C.; Mazarrotto, Giovanny A. C. A.; Gonçalves, Giselle M.; Zuliani, Juliana P.; Calderon, Leonardo A.; Soares, Andreimar M.; Pereira da Silva, Luiz H.; Duarte dos Santos, Claudia N.; Fernandes, Carla F. C.; Stabeli, Rodrigo G.

2014-01-01

In addition to conventional antibodies, camelids produce immunoglobulins G composed exclusively of heavy chains in which the antigen binding site is formed only by single domains called VHH. Their particular characteristics make VHHs interesting tools for drug-delivery, passive immunotherapy and high-throughput diagnosis. Hantaviruses are rodent-borne viruses of the Bunyaviridae family. Two clinical forms of the infection are known. Hemorrhagic Fever with Renal Syndrome (HFRS) is present in the Old World, while Hantavirus Pulmonary Syndrome (HPS) is found on the American continent. There is no specific treatment for HPS and its diagnosis is carried out by molecular or serological techniques, using mainly monoclonal antibodies or hantavirus nucleoprotein (N) to detect IgM and IgG in patient serum. This study proposes the use of camelid VHHs to develop alternative methods for diagnosing and confirming HPS. Phage display technology was employed to obtain VHHs. After immunizing one Lama glama against the recombinant N protein (prNΔ85) of a Brazilian hantavirus strain, VHH regions were isolated to construct an immune library. VHHs were displayed fused to the M13KO7 phage coat protein III and the selection steps were performed on immobilized prNΔ85. After selection, eighty clones recognized specifically the N protein. These were sequenced, grouped based mainly on the CDRs, and five clones were analyzed by western blot (WB), surface plasmon resonance (SPR) device, and ELISA. Besides the ability to recognize prNΔ85 by WB, all selected clones showed affinity constants in the nanomolar range. Additionaly, the clone KC329705 is able to detect prNΔ85 in solution, as well as the native viral antigen. Findings support the hypothesis that selected VHHs could be a powerful tool in the development of rapid and accurate HPS diagnostic assays, which are essential to provide supportive care to patients and reduce the high mortality rate associated with hantavirus infections. PMID

[Hantavirus infection as the cause of haemorrhagic fever with renal syndrome].

PubMed

Redal-Baigorri, Belén; Chen Nielsen, Xiaohui; Martin-Iguacel, Raquel

2012-10-29

Hantavirus is an RNA virus that can cause potentially fatal pulmonary and renal diseases in humans. Infections with Hantaviruses occur through inhalation of aerosol from rodent faeces, urine or saliva. The predominant virus type in Denmark is the Puumala virus, which causes the mildest form of haemorrhagic fever with renal syndrome, the so-called nephropathia epidemica (NE) with good prognosis (mortality 0.1-0.4%). The incidence of Hantavirus-infection in Denmark is about ten cases a year. The diagnosis of Hantavirus-infection is based on serology and/or polymerase chain reaction in blood or urine.

High-resolution computed tomography findings in eight patients with hantavirus pulmonary syndrome.

PubMed

Barbosa, Diego de Lacerda; Hochhegger, Bruno; Souza, Arthur Soares; Zanetti, Gláucia; Escuissato, Dante Luiz; Meirelles, Gustavo de Souza Portes; Funari, Marcelo Buarque de Gusmão; Marchiori, Edson

2017-01-01

The purpose of this study was to describe the high-resolution computed tomography (HRCT) findings in patients with hantavirus pulmonary syndrome (HPS). We retrospectively reviewed HRCT findings from eight cases of HPS. All patients were men, aged 19-70 (mean, 41.7) years. Diagnoses were established by serological test (enzyme-linked immunosorbent assay) in all patients. Two chest radiologists analyzed the images and reached decisions by consensus. The predominant HRCT findings were ground-glass opacities (GGOs) and smooth inter- and intralobular septal thickening, found in all eight cases; however, the crazy-paving pattern was found in only three cases. Pleural effusion and peribronchovascular thickening were observed in five patients. The abnormalities were bilateral in all patients. The predominant HRCT findings in patients with HPS were GGOs and smooth inter- and intralobular septal thickening, which probably correlate with the histopathologic findings of pulmonary edema.

Serum Cytokine Profiles Differentiating Hemorrhagic Fever with Renal Syndrome and Hantavirus Pulmonary Syndrome.

PubMed

Khaiboullina, Svetlana F; Levis, Silvana; Morzunov, Sergey P; Martynova, Ekaterina V; Anokhin, Vladimir A; Gusev, Oleg A; St Jeor, Stephen C; Lombardi, Vincent C; Rizvanov, Albert A

2017-01-01

Hantavirus infection is an acute zoonosis that clinically manifests in two primary forms, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). HFRS is endemic in Europe and Russia, where the mild form of the disease is prevalent in the Tatarstan region. HPS is endemic in Argentina, as well as other countries of North and South American. HFRS and HPS are usually acquired via the upper respiratory tract by inhalation of virus-contaminated aerosol. Although the pathogenesis of HFRS and HPS remains largely unknown, postmortem tissue studies have identified endothelial cells as the primary target of infection. Importantly, cell damage due to virus replication, or subsequent tissue repair, has not been documented. Since no single factor has been identified that explains the complexity of HFRS or HPS pathogenesis, it has been suggested that a cytokine storm may play a crucial role in the manifestation of both diseases. In order to identify potential serological markers that distinguish HFRS and HPS, serum samples collected during early and late phases of the disease were analyzed for 48 analytes using multiplex magnetic bead-based assays. Overall, serum cytokine profiles associated with HPS revealed a more pro-inflammatory milieu as compared to HFRS. Furthermore, HPS was strictly characterized by the upregulation of cytokine levels, in contrast to HFRS where cases were distinguished by a dichotomy in serum cytokine levels. The severe form of hantavirus zoonosis, HPS, was characterized by the upregulation of a higher number of cytokines than HFRS (40 vs 21). In general, our analysis indicates that, although HPS and HFRS share many characteristic features, there are distinct cytokine profiles for these diseases. These profiles suggest a strong activation of an innate immune and inflammatory responses are associated with HPS, relative to HFRS, as well as a robust activation of Th1-type immune responses. Finally, the results of our analysis

A novel Sin Nombre virus DNA vaccine and its inclusion in a candidate pan-hantavirus vaccine against hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS).

PubMed

Hooper, Jay W; Josleyn, Matthew; Ballantyne, John; Brocato, Rebecca

2013-09-13

Sin Nombre virus (SNV; family Bunyaviridae, genus Hantavirus) causes a hemorrhagic fever known as hantavirus pulmonary syndrome (HPS) in North America. There have been approximately 200 fatal cases of HPS in the United States since 1993, predominantly in healthy working-age males (case fatality rate 35%). There are no FDA-approved vaccines or drugs to prevent or treat HPS. Previously, we reported that hantavirus vaccines based on the full-length M gene segment of Andes virus (ANDV) for HPS in South America, and Hantaan virus (HTNV) and Puumala virus (PUUV) for hemorrhagic fever with renal syndrome (HFRS) in Eurasia, all elicited high-titer neutralizing antibodies in animal models. HFRS is more prevalent than HPS (>20,000 cases per year) but less pathogenic (case fatality rate 1-15%). Here, we report the construction and testing of a SNV full-length M gene-based DNA vaccine to prevent HPS. Rabbits vaccinated with the SNV DNA vaccine by muscle electroporation (mEP) developed high titers of neutralizing antibodies. Furthermore, hamsters vaccinated three times with the SNV DNA vaccine using a gene gun were completely protected against SNV infection. This is the first vaccine of any kind that specifically elicits high-titer neutralizing antibodies against SNV. To test the possibility of producing a pan-hantavirus vaccine, rabbits were vaccinated by mEP with an HPS mix (ANDV and SNV plasmids), or HFRS mix (HTNV and PUUV plasmids), or HPS/HFRS mix (all four plasmids). The HPS mix and HFRS mix elicited neutralizing antibodies predominantly against ANDV/SNV and HTNV/PUUV, respectively. Furthermore, the HPS/HFRS mix elicited neutralizing antibodies against all four viruses. These findings demonstrate a pan-hantavirus vaccine using a mixed-plasmid DNA vaccine approach is feasible and warrants further development. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Hantavirus Prevention: Cleanup of Rodent Contamination

DTIC Science & Technology

2008-09-01

Hantaviruses in the Americas may cause human disease involving the lungs, hence the name " hantavirus pulmonary syndrome" (HPS). Since May 1993, a...humans are also found in other rodents, but the number of cases stemming from these hantaviruses is small when compared to SNV. Hantavirus is shed in... HANTAVIRUS PREVENTION: CLEANUP OF RODENT CONTAMINATION Technical Information Paper 18-001-0306

A Fatal Hantavirus Pulmonary Syndrome Misdiagnosed as Dengue: An Investigation into the First Reported Case in Rio de Janeiro State, Brazil.

PubMed

de Oliveira, Renata Carvalho; Guterres, Alexandro; Teixeira, Bernardo Rodrigues; Fernandes, Jorlan; Júnior, João Marcos Penna; de Jesus Oliveira Júnior, Reynaldo; Pereira, Liana Strecht; Júnior, João Bosco; Meneguete, Patrícia Soares; Dias, Cristina Maria Giordano; Bonvicino, Cibele Rodrigues; D'Andrea, Paulo Sérgio; de Lemos, Elba Regina Sampaio

2017-07-01

We report the results of an investigation into a fatal case of hantavirus pulmonary syndrome (HPS) in Rio de Janeiro State, Brazil, where the disease had not been reported previous to 2015. Following the notification of an HPS case, serum samples were collected from the household members and work contacts of the HPS patient and tested for antibody to hantaviruses. Seroprevalence of 22% (10/45) was indicated for hantavirus out of 45 human samples tested. Blood and tissue samples were collected from 72 rodents during fieldwork to evaluate the prevalence of hantavirus infection, by using enzyme-linked immunosorbent assay IgG, and to characterize the rodent hantavirus reservoir(s), by reverse transcription polymerase chain reaction and sequencing. Antibody prevalence was 6.9%. The circulation of a single genotype, the Juquitiba hantavirus, carried by two rodent species, black-footed pigmy rice rat ( Oligoryzomys nigripes ) and cursor grass mouse ( Akodon cursor ), was shown by analysis of the nucleotide sequences of the S segment. Juquitiba hantavirus circulates in rodents of various species, but mainly in the black-footed pigmy rice rat. HPS is a newly recognized clinical entity in Rio de Janeiro State and should be considered in patients with febrile illness and acute respiratory distress.

The role of endothelial activation in dengue hemorrhagic fever and hantavirus pulmonary syndrome.

PubMed

Spiropoulou, Christina F; Srikiatkhachorn, Anon

2013-08-15

The loss of the endothelium barrier and vascular leakage play a central role in the pathogenesis of hemorrhagic fever viruses. This can be caused either directly by the viral infection and damage of the vascular endothelium, or indirectly by a dysregulated immune response resulting in an excessive activation of the endothelium. This article briefly reviews our knowledge of the importance of the disruption of the vascular endothelial barrier in two severe disease syndromes, dengue hemorrhagic fever and hantavirus pulmonary syndrome. Both viruses cause changes in vascular permeability without damaging the endothelium. Here we focus on our understanding of the virus interaction with the endothelium, the role of the endothelium in the induced pathogenesis, and the possible mechanisms by which each virus causes vascular leakage. Understanding the dynamics between viral infection and the dysregulation of the endothelial cell barrier will help us to define potential therapeutic targets for reducing disease severity.

Hantavirus-infection Confers Resistance to Cytotoxic Lymphocyte-Mediated Apoptosis

PubMed Central

Gupta, Shawon; Braun, Monika; Tischler, Nicole D.; Stoltz, Malin; Sundström, Karin B.; Björkström, Niklas K.; Ljunggren, Hans-Gustaf; Klingström, Jonas

2013-01-01

Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardio-pulmonary syndrome (HCPS; also called hantavirus pulmonary syndrome (HPS)), both human diseases with high case-fatality rates. Endothelial cells are the main targets for hantaviruses. An intriguing observation in patients with HFRS and HCPS is that on one hand the virus infection leads to strong activation of CD8 T cells and NK cells, on the other hand no obvious destruction of infected endothelial cells is observed. Here, we provide an explanation for this dichotomy by showing that hantavirus-infected endothelial cells are protected from cytotoxic lymphocyte-mediated induction of apoptosis. When dissecting potential mechanisms behind this phenomenon, we discovered that the hantavirus nucleocapsid protein inhibits the enzymatic activity of both granzyme B and caspase 3. This provides a tentative explanation for the hantavirus-mediated block of cytotoxic granule-mediated apoptosis-induction, and hence the protection of infected cells from cytotoxic lymphocytes. These findings may explain why infected endothelial cells in hantavirus-infected patients are not destroyed by the strong cytotoxic lymphocyte response. PMID:23555267

The role of endothelial activation in dengue hemorrhagic fever and hantavirus pulmonary syndrome

PubMed Central

Spiropoulou, Christina F; Srikiatkhachorn, Anon

2013-01-01

The loss of the endothelium barrier and vascular leakage play a central role in the pathogenesis of hemorrhagic fever viruses. This can be caused either directly by the viral infection and damage of the vascular endothelium, or indirectly by a dysregulated immune response resulting in an excessive activation of the endothelium. This article briefly reviews our knowledge of the importance of the disruption of the vascular endothelial barrier in two severe disease syndromes, dengue hemorrhagic fever and hantavirus pulmonary syndrome. Both viruses cause changes in vascular permeability without damaging the endothelium. Here we focus on our understanding of the virus interaction with the endothelium, the role of the endothelium in the induced pathogenesis, and the possible mechanisms by which each virus causes vascular leakage. Understanding the dynamics between viral infection and the dysregulation of the endothelial cell barrier will help us to define potential therapeutic targets for reducing disease severity. PMID:23841977

Presence of hantavirus in small mammals of the Ouachita Mountains

Treesearch

Roger W. Perry; Ronald E. Thill; Philip A. Tappe; M. Anthony Melchiors

1997-01-01

In 1993, an outbreak of human hantavirus pulmonary syndrome (HPS) occurred in the southwestern United States causing severe pulmonary dysfunction and death among most of those infected. Shortly after the outbreak, the causative agent was identified as the Sin Nombre virus (SNV), a virus of the genus Hantavirus. Several hantaviruses have since been identified in North...

Hantavirus Reservoir Hosts Associated with Peridomestic Habitats in Argentina

PubMed Central

Pini, Noemí; Bolpe, Jorge; Levis, Silvana; Mills, James; Segura, Elsa; Guthmann, Nadia; Cantoni, Gustavo; Becker, José; Fonollat, Ana; Ripoll, Carlos; Bortman, Marcelo; Benedetti, Rosendo; Sabattini, Marta; Enria, Delia

1999-01-01

Five species of sigmodontine rodents have been identified in Argentina as the putative reservoirs of six circulating hantavirus genotypes. Two species of Oligoryzomys are associated with the genotypes causing hantavirus pulmonary syndrome, Oligoryzomys flavescens for Lechiguanas and O. longicaudatus for Andes and Oran genotypes. Reports of human cases of hantavirus pulmonary syndrome prompted rodent trapping (2,299 rodents of 32 species during 27,780 trap nights) at potential exposure sites in three disease-endemic areas. Antibody reactive to Sin Nombre virus was found in six species, including the known hantavirus reservoir species. Risk for peridomestic exposure to host species that carry recognized human pathogens was high in all three major disease-endemic areas. PMID:10603213

Neutrophil Depletion Suppresses Pulmonary Vascular Hyperpermeability and Occurrence of Pulmonary Edema Caused by Hantavirus Infection in C.B-17 SCID Mice

PubMed Central

Koma, Takaaki; Yoshimatsu, Kumiko; Nagata, Noriyo; Sato, Yuko; Shimizu, Kenta; Yasuda, Shumpei P.; Amada, Takako; Nishio, Sanae; Hasegawa, Hideki

2014-01-01

ABSTRACT Hantavirus infections are characterized by vascular hyperpermeability and neutrophilia. However, the pathogenesis of this disease is poorly understood. Here, we demonstrate for the first time that pulmonary vascular permeability is increased by Hantaan virus infection and results in the development of pulmonary edema in C.B-17 severe combined immunodeficiency (SCID) mice lacking functional T cells and B cells. Increases in neutrophils in the lung and blood were observed when pulmonary edema began to be observed in the infected SCID mice. The occurrence of pulmonary edema was inhibited by neutrophil depletion. Moreover, the pulmonary vascular permeability was also significantly suppressed by neutrophil depletion in the infected mice. Taken together, the results suggest that neutrophils play an important role in pulmonary vascular hyperpermeability and the occurrence of pulmonary edema after hantavirus infection in SCID mice. IMPORTANCE Although hantavirus infections are characterized by the occurrence of pulmonary edema, the pathogenic mechanism remains largely unknown. In this study, we demonstrated for the first time in vivo that hantavirus infection increases pulmonary vascular permeability and results in the development of pulmonary edema in SCID mice. This novel mouse model for human hantavirus infection will be a valuable tool and will contribute to elucidation of the pathogenetic mechanisms. Although the involvement of neutrophils in the pathogenesis of hantavirus infection has largely been ignored, the results of this study using the mouse model suggest that neutrophils are involved in the vascular hyperpermeability and development of pulmonary edema in hantavirus infection. Further study of the mechanisms could lead to the development of specific treatment for hantavirus infection. PMID:24719427

Differences between Human and Rodent Plasmacytoid Dendritic Cells May Explain the Pathogenic Disparity of Hantavirus Infection

DTIC Science & Technology

2016-06-01

cause two acute febrile diseases in humans: hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardio-pulmonary syndrome (HCPS). The purpose...of Biochemistry, School of Medicine, University of Nevada, Reno, NV, USA Hantavirus pulmonary syndrome (HPS) is an acute zoonotic disease transmitted...bling acute respiratory distress syndrome (10). Rapidly progress- ing pulmonary edema, myocardial depression, and hypovolemia are the leading cause of

Hantavirus pulmonary syndrome: prognostic factors for death in reported cases in Brazil.

PubMed

da Rosa Elkhoury, Mauro; da Silva Mendes, Wellington; Waldman, Eliseu Alves; Dias, Juarez Pereira; Carmo, Eduardo Hage; Fernando da Costa Vasconcelos, Pedro

2012-05-01

Hantavirus pulmonary syndrome (HPS) was described for the first time in Brazil in 1993 and has occurred endemically throughout the country. This study analysed clinical and laboratory aspects as well as death-related factors for HPS cases in Brazil from 1993 to 2006. The investigation comprised a descriptive and exploratory study of the history of cases as well as an analytical retrospective cohort survey to identify prognostic factors for death due to HPS. A total of 855 Brazilian HPS cases were assessed. The majority of cases occurred during spring (33.5%) and winter (27.6%), mainly among young male adults working in rural areas. The global case fatality rate was 39.3%. The mean interval between the onset of symptoms and hospitalisation was 4 days and that between hospitalisation and death was 1 day. In the multiple regression analysis, adult respiratory distress syndrome and mechanical respiratory support were associated with risk of death; when these two variables were excluded from the model, dyspnoea and haemoconcentration were associated with a higher risk of death. Copyright © 2012 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Discovery of hantaviruses in bats and insectivores and the evolution of the genus Hantavirus.

PubMed

Zhang, Yong-Zhen

2014-07-17

Hantaviruses are among the most important zoonotic pathogens of humans, causing either hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). From the period 1964-2006 almost all hantaviruses had been identified in rodents, with the exception of Thottapalayam virus (TPMV) isolated from shrews sampled in India. As a consequence, rodents were considered as the natural reservoir hosts. However, over the past seven years, most of the newly found hantavirus genotypes have been from either shrews or moles. Remarkably, in recent years divergent hantaviruses have also been identified in bats sampled from both Africa and Asia. All these data indicate that hantaviruses have a broad range of natural reservoir hosts. Phylogenetic analyses of the available sequences of hantaviruses suggest that hantaviruses might have first appeared in Chiroptera (bats) or Soricomorpha (moles and shrews), before emerging in rodent species. Although rodent hantaviruses cluster according to whether their hosts are members of the Murinae and Cricetidae, the phylogenetic histories of the viruses are not always congruent with those of their hosts, indicating that cross-species transmission events have occurred at all taxonomic levels. In sum, both cross-species transmission and co-divergence have produced the high genetic diversity of hantaviruses described to date. Copyright © 2014. Published by Elsevier B.V.

A lethal disease model for New World hantaviruses using immunosuppressed Syrian hamsters.

PubMed

Vergote, Valentijn; Laenen, Lies; Vanmechelen, Bert; Van Ranst, Marc; Verbeken, Erik; Hooper, Jay W; Maes, Piet

2017-10-01

Hantavirus, the hemorrhagic causative agent of two clinical diseases, is found worldwide with variation in severity, incidence and mortality. The most lethal hantaviruses are found on the American continent where the most prevalent viruses like Andes virus and Sin Nombre virus are known to cause hantavirus pulmonary syndrome. New World hantavirus infection of immunocompetent hamsters results in an asymptomatic infection except for Andes virus and Maporal virus; the only hantaviruses causing a lethal disease in immunocompetent Syrian hamsters mimicking hantavirus pulmonary syndrome in humans. Hamsters, immunosuppressed with dexamethasone and cyclophosphamide, were infected intramuscularly with different New World hantavirus strains (Bayou virus, Black Creek Canal virus, Caño Delgadito virus, Choclo virus, Laguna Negra virus, and Maporal virus). In the present study, we show that immunosuppression of hamsters followed by infection with a New World hantavirus results in an acute disease that precisely mimics both hantavirus disease in humans and Andes virus infection of hamsters. Infected hamsters showed specific clinical signs of disease and moreover, histological analysis of lung tissue showed signs of pulmonary edema and inflammation within alveolar septa. In this study, we were able to infect immunosuppressed hamsters with different New World hantaviruses reaching a lethal outcome with signs of disease mimicking human disease.

Hantavirus pulmonary syndrome and rodent reservoirs in the savanna-like biome of Brazil's southeastern region.

PubMed

Limongi, J E; Oliveira, R C; Guterres, A; Costa Neto, S F; Fernandes, J; Vicente, L H B; Coelho, M G; Ramos, V N; Ferreira, M S; Bonvicino, C R; D'Andrea, P S; Lemos, E R S

2016-04-01

This paper describes the diversity of rodent fauna in an area endemic for hantavirus cardiopulmonary syndrome (HCPS) in Brazil, the population dynamics and the relationship of rodents with hantavirus in the Cerrado (savanna-like) biome. Additionally, an analysis is made of the partial S segment sequences of the hantaviruses obtained from serologically confirmed human HCPS cases and from rodent specimens. Rodents were collected during four campaigns. Human serum samples were collected from suspected cases of HCPS at hospitals in the state of Minas Gerais. The samples antibody-reactive by ELISA were processed by RT-PCR. The PCR product was amplified and sequenced. Hantavirus was detected only in Necromys lasiurus, the wild rodent species most prevalent in the Cerrado biome (min-max: 50-83·7%). All the six human serum samples were hantavirus seropositive and five showed amplified PCR products. The analysis of the nucleotide sequences showed the circulation of a single genotype, the Araraquara hantavirus. The environmental changes that have occurred in the Cerrado biome in recent decades have favoured N. lasiurus in interspecific competition of habitats, thus increasing the risk of contact between humans and rodent species infected with hantavirus. Our data corroborate the definition of N. lasiurus as the main hantavirus reservoir in the Cerrado biome.

Role of mixed Th1 and Th2 serum cytokines on pathogenesis and prognosis of hantavirus pulmonary syndrome.

PubMed

Borges, Alessandra Abel; Campos, Gelse Mazzoni; Moreli, Marcos Lázaro; Moro Souza, Ricardo Luiz; Saggioro, Fabiano Pinto; Figueiredo, Glauciane Garcia; Livonesi, Márcia Cristina; Moraes Figueiredo, Luiz Tadeu

2008-01-01

The hantavirus pulmonary syndrome (HPS) is an emerging syndrome in the Americas. The disease results from intense immune activation and changes in vascular permeability. The aim of this study was to determine the profile of serum cytokines in HPS patients looking for correlation with the clinical parameters, severity and outcome of illness. Studying 21 HPS patients, we found that IL-6 may have an important role in the pathogenesis of HPS, being associated with fatal outcome. Our results also support a mixed Th1/Th2 immune response during the course of HPS and that the magnitude of Th1 response effector cytokines is correlated to HPS severity. The decreased levels of TGF-beta observed in HPS patients suggest that immunoregulatory activity could be damaged in these patients.

Hantaviruses and cardiopulmonary syndrome in South America.

PubMed

Figueiredo, Luiz Tadeu Moraes; Souza, William Marciel de; Ferrés, Marcela; Enria, Delia Alcira

2014-07-17

Hantavirus (Bunyaviridae) cardiopulmonary syndrome (HCPS) is an emerging health problem in South America due to urban growth and to the expansion of agriculture and cattle-raising areas into ecosystems containing most of the species of Sigmodontinae rodents that act as hantavirus reservoirs. About 4000 HCPS cases have been reported in South America up to 2013, associated with the following hantaviruses: Andes, Anajatuba, Araraquara (ARQV), Paranoá, Bermejo, Castelo dos Sonhos, Juquitiba, Araucária, Laguna Negra, Lechiguanas, Maripa, Oran, Rio Mamore and Tunari. The transmission of hantavirus to man occurs by contact with or through aerosols of excreta and secretions of infected rodents. Person-to-person transmission of hantavirus has also been reported in Argentina and Chile. HCPS courses with a capillary leaking syndrome produced by the hantavirus infecting lung endothelial cells and mostly with a severe inflammatory process associated with a cytokine storm. HCPS starts as a dengue-like acute febrile illness but after about 3 days progresses to respiratory failure and cardiogenic shock, leading to a high fatality rate that reaches 50% for patients infected with ARQV. Copyright © 2014 Elsevier B.V. All rights reserved.

[Cardiopulmonary syndrome in hantavirus infection (an overview)].

PubMed

Mukhetdinova, G A; Fazlyeva, R M; Fazlyev, M M

2012-06-01

The article provides an overview of domestic and foreign literature on modern aspects of hantavirus infection. Hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome have a high epidemiological significance for Russia's Armed Forces and the armies of many foreign countries. Current knowledge of the various manifestations of the disease contribute to the improvement of diagnosis and timely delivery of medical and preventive measures.

Pathogenic Hantaviruses, Northeastern Argentina and Eastern Paraguay

PubMed Central

Martinez, Valeria P.; Bellomo, Carla; Maidana, Silvina; San Juan, Jorge; Tagliaferri, Paulina; Bargardi, Severino; Vazquez, Cynthia; Colucci, Norma; Estévez, Julio; Almiron, María

2007-01-01

We describe the first, to our knowledge, cases of hantavirus pulmonary syndrome in northeastern Argentina and eastern Paraguay. Andes and Juquitiba (JUQ) viruses were characterized. JUQV was also confirmed in 5 Oligoryzomys nigripes reservoir species from Misiones. A novel Akodon-borne genetic hantavirus lineage was detected in 1 rodent from the Biologic Reserve of Limoy. PMID:17953094

Detection of different South American hantaviruses.

PubMed

Guterres, Alexandro; de Oliveira, Renata Carvalho; Fernandes, Jorlan; Schrago, Carlos Guerra; de Lemos, Elba Regina Sampaio

2015-12-02

Hantaviruses are the etiologic agents of Hemorrhagic Fever with Renal Syndrome (HFRS) in Old World, and Hantavirus Pulmonary Syndrome (HPS)/Hantavirus Cardiopulmonary Syndrome (HCPS), in the New World. Serological methods are the most common approach used for laboratory diagnosis of HCPS, however theses methods do not allow the characterization of viral genotypes. The polymerase chain reaction (PCR) has been extensively used for diagnosis of viral infections, including those caused by hantaviruses, enabling detection of few target sequence copies in the sample. However, most studies proposed methods of PCR with species-specific primers. This study developed a simple and reliable diagnostic system by RT-PCR for different hantavirus detection. Using new primers set, we evaluated human and rodent hantavirus positive samples of various regions from Brazil. Besides, we performed computational analyzes to evaluate the detection of other South American hantaviruses. The diagnostic system by PCR proved to be a sensible and simple assay, allowing amplification of Juquitiba virus, Araraquara virus, Laguna Negra virus, Rio Mamore virus and Jabora virus, beyond of the possibility of the detecting Andes, Anajatuba, Bermejo, Choclo, Cano Delgadito, Lechiguanas, Maciel, Oran, Pergamino and Rio Mearim viruses. The primers sets designed in this study can detect hantaviruses from almost all known genetics lineages in Brazil and from others South America countries and also increases the possibility to detect new hantaviruses. These primers could easily be used both in diagnosis of suspected hantavirus infections in humans and also in studies with animals reservoirs. Copyright © 2015 Elsevier B.V. All rights reserved.

Twenty years of hantavirus pulmonary syndrome in Brazil: a review of epidemiological and clinical aspects.

PubMed

Pinto Junior, Vitor Laerte; Hamidad, Amani Moura; Albuquerque Filho, Dalcy de Oliveira; dos Santos, Vitorino Modesto

2014-02-13

Hantavirus infection is transmitted to humans by wild rodents and the most common clinical form in Brazil is the Hantavirus Pulmonary Syndrome (HPS). The first serological evidence of the disease was identified in 1990, in Recife, Pernambuco State, and later in 1993 in Juquitiba, State of São Paulo. Since then there has been a progressive increase in case notification in all regions of the country. The clinical aspects of the disease in Brazil are characterized by a prodromal phase, with nonspecific signs and symptoms of an acute febrile illness. After about three days, respiratory distress develops, accompanied by dry cough that turns progressively productive, evolving to dyspnea and respiratory failure with cardiogenic shock. Although the majority of patients receive hospital care in intensive care therapy units, case-fatality rate in Brazil ranges from 33% to 100% depending on the region. Besides it has to be added the problem of differential diagnosis with other prevalent diseases in the country, like dengue and leptospirosis. Questions about the impact of uncontrolled urbanization and other environmental changes caused by human action have been raised. Due to increasing incidence and high case-fatality, there is an urge to respond to such questions to recommend preventative measures. This article aims to review the main acquisitions in clinical and epidemiological knowledge about HPS in Brazil in the last twenty years.

Tula hantavirus infection in immunocompromised host, Czech Republic.

PubMed

Zelená, Hana; Mrázek, Jakub; Kuhn, Tomáš

2013-11-01

We report molecular evidence of Tula hantavirus as an etiologic agent of pulmonary-renal syndrome in an immunocompromised patient. Acute hantavirus infection was confirmed by using serologic and molecular methods. Sequencing revealed Tula virus genome RNA in the patient's blood. This case shows that Tula virus can cause serious disease in humans.

Hantavirus pulmonary syndrome clinical findings: evaluating a surveillance case definition.

PubMed

Knust, Barbara; Macneil, Adam; Rollin, Pierre E

2012-05-01

Clinical cases of hantavirus pulmonary syndrome (HPS) can be challenging to differentiate from other acute respiratory diseases, which can lead to delays in diagnosis, treatment, and disease reporting. Rapid onset of severe disease occurs, at times before diagnostic test results are available. This study's objective was to examine the clinical characteristics of patients that would indicate HPS to aid in detection and reporting. Test results of blood samples from U.S. patients suspected of having HPS submitted to the Centers for Disease Control and Prevention from 1998-2010 were reviewed. Patient information collected by case report forms was compared between HPS-confirmed and test-negative patients. Diagnostic sensitivity, specificity, predictive values, and likelihood ratios were calculated for individual clinical findings and combinations of variables. Of 567 patients included, 36% were HPS-confirmed. Thrombocytopenia, chest x-rays with suggestive signs, and receiving supplemental oxygenation were highly sensitive (>95%), while elevated hematocrit was highly specific (83%) in detecting HPS. Combinations that maximized sensitivity required the presence of thrombocytopenia. Using a national sample of suspect patients, we found that thrombocytopenia was a highly sensitive indicator of HPS and should be included in surveillance definitions for suspected HPS. Using a sensitive suspect case definition to identify potential HPS patients that are confirmed by highly specific diagnostic testing will ensure accurate reporting of this disease.

[Morphological findings in fatal cases of hantavirus cardiopulmonary syndrome. Report of 7 autopsies].

PubMed

Guzmán G, Pablo; Tapia E, Oscar; Villaseca H, Miguel; Araya O, Juan; Antonio P, Lilia; Lee O, Bolívar; Roa S, Juan

2010-10-01

Hantavirus cardiopulmonary syndrome (HCPS) is an acute infectious disease characterized by sudden cardiorespiratory failure and high mortality, caused by a RNA virus of the genus Hantavirus, family Bunyaviridae, 15% of Chilean cases have been detected in the Araucania Region. To determine in fatal cases of HCPS, clinical and morphological characteristics. Descriptive-retrospective analysis of seven fatal cases with postmortem study of HCPS, attended between 1997 and 2009 at the Hospital of Temuco, Chile. Cases were young patients from rural areas, and presented as an illness of progressive respiratory failure, with leukocytosis, thrombocytopenia and bilateral interstitial pulmonary infiltrates. Main morphological findings were marked intersticial and intraalveolar pulmonary edema, with minimal epithelial injury and mononuclear cell intersticial infiltrate and mild edematous intersticial inflamatory process. Epidemiological, clinical and laboratory background allow to suspect HCPS. In fatal cases, the autopsy makes possible to discard other similar pathologies and provide tissue for confirmation of the disease.

[Geographic expansion of hantavirus pulmonary syndrome in Argentina. The southernest case report].

PubMed

Bellomo, Carla; Nudelman, Julio; Kwaszka, Roberto; Vazquez, Gabriela; Cantoni, Gustavo; Weinzettel, Barbara; Larrieu, Edmundo G; Padula, Paula

2009-01-01

Since 1995 more than 1000 cases of hantavirus pulmonary syndrome (HPS) were reported in Argentina, a severe disease and often fatal to humans. Most cases were associated with Andes virus (AND) that caused few events of person-to-person transmission. Several lineages of pathogenic AND viruses have been described, including AND South, hosted by the rodent Oligoryzomys longicaudatus which affects the Patagonian region of Argentina and Chile. We studied the clinical and epidemiological characteristics of a HPS case. The objective was to describe the clinical presentation of the case, its epidemiology, the likely site of infection, the viral variant implicated and its relationship with the closest reported cases. We carried out the clinical follow up, serological and molecular diagnosis and the epidemiological research, including a rodent reservoir study. The clinical presentation of the case was the classical and moderate, caused by AND South virus. Its viral nucleotide sequence was compared with cases from Southern Argentina and Chile. This case was found to be the most Southern (48 degrees 46' 1.2'' S; 70 degrees 15' O) case reported and involved a new Argentinean province.

Diagnosing and Treating Hantavirus Pulmonary Syndrome (HPS)

MedlinePlus

... and mention their potential rodent exposure. Are there any complications? Previous observations of patients that develop HPS from New World Hantaviruses recover completely. No chronic infection has been ...

Hantavirus in Indian Country: The First Decade in Review

ERIC Educational Resources Information Center

Pottinger, Richard

2005-01-01

Hantavirus, caused due to close contact with mice in a dwelling, first emerged in the spring of 1993 on the Navajo Reservation and although it is by no means an Indian disease, there are four times as many cases of hantavirus pulmonary syndrome (HPS) among non-Indians. Inadequate rural housing, especially common in western Indian Country,…

How People Get Hantavirus Pulmonary Syndrome (HPS)

MedlinePlus

... US. The Black Creek hantavirus, carried by the cotton rat , is found in the southeastern US. Cases ... In the United States, deer mice (along with cotton rats and rice rats in the southeastern states ...

Antiviral efficacy of favipiravir against two prominent etiological agents of hantavirus pulmonary syndrome.

PubMed

Safronetz, David; Falzarano, Darryl; Scott, Dana P; Furuta, Yousuke; Feldmann, Heinz; Gowen, Brian B

2013-10-01

Hantavirus pulmonary syndrome (HPS) is caused by infection with several Sigmodontinae- and Neotominae-borne hantaviruses and has a case fatality rate of 30 to 50%. Humans often become infected by inhalation of materials contaminated with virus-laden rodent urine or saliva, although human-to-human transmission has also been documented for Andes virus (ANDV). The ability to transmit via aerosolization, coupled with the high mortality rates and lack of therapeutic options, makes the development of medical countermeasures against HPS imperative. In the present study, we evaluated the efficacy of the broad-spectrum antiviral agent favipiravir (T-705) against Sin Nombre virus (SNV) and ANDV, the predominant causes of HPS in North and South America, respectively. In vitro, T-705 potently inhibited SNV and ANDV, as evidenced by decreased detection of viral RNA and reduced infectious titers. For both viruses, the 90% effective concentration was estimated at ≤5 μg/ml (≤31.8 μM). In the lethal ANDV hamster model, daily administration of oral T-705 at 50 or 100 mg/kg of body weight diminished the detection of viral RNA and antigen in tissue specimens and significantly improved survival rates. Oral T-705 therapy remained protective against HPS when treatment was initiated prior to the onset of viremia. No disease model for SNV exists; however, using a hamster-adapted SNV, we found that daily administration of oral T-705 significantly reduced the detection of SNV RNA and antigen in tissue specimens, suggesting that the compound would also be effective against HPS in North America. Combined, these results suggest that T-705 treatment is beneficial for postexposure prophylaxis against HPS-causing viruses and should be considered for probable exposures.

Twenty-year summary of surveillance for human hantavirus infections, United States.

PubMed

Knust, Barbara; Rollin, Pierre E

2013-12-01

In the past 20 years of surveillance for hantavirus in humans in the United States, 624 cases of hantavirus pulmonary syndrome (HPS) have been reported, 96% of which occurred in states west of the Mississippi River. Most hantavirus infections are caused by Sin Nombre virus, but cases of HPS caused by Bayou, Black Creek Canal, Monongahela, and New York viruses have been reported, and cases of domestically acquired hemorrhagic fever and renal syndrome caused by Seoul virus have also occurred. Rarely, hantavirus infections result in mild illness that does not progress to HPS. Continued testing and surveillance of clinical cases in humans will improve our understanding of the etiologic agents involved and the spectrum of diseases.

Imported hantavirus cardiopulmonary syndrome in an Italian traveller returning from Cuba.

PubMed

Rovida, Francesca; Percivalle, Elena; Sarasini, Antonella; Chichino, Guido; Baldanti, Fausto

2013-01-01

Hantavirus hemorrhagic fever with renal syndrome is endemic in Europe and Asia, while hantavirus cardiopulmonary syndrome (HCPS) is endemic in Northern, Central and Southern America. The first case of imported HCPS involving an Italian traveller returning from Cuba is reported.

Hantavirus cardiopulmonary syndrome due to Puumala virus in Germany.

PubMed

Vollmar, Patrick; Lubnow, Matthias; Simon, Michaela; Müller, Thomas; Bergler, Tobias; Alois, Philipp; Thoma, Bryan R; Essbauer, Sandra

2016-11-01

In Germany Puumala virus (PUUV), known to cause mild forms of hemorrhagic fever with renal syndrome (HFRS), is the predominating endemic hantavirus. We herein describe an unusually severe case of a PUUV infection that occurred in summer 2015 in South Eastern Germany in a region known to be endemic for PUUV since over ten years. A 54-year-old female gardener was admitted to hospital with fever, cough and dyspnea. Within 48hours the patient developed a rapid progressive adult respiratory distress syndrome (ARDS) with circulatory failure and required ECMO (extracorporeal membrane oxygenation) treatment. Serological and molecular biological examinations of serum samples confirmed an infection with PUUV. Partial sequences of the S- and M-segment clustered to a strain previously described in South Eastern Germany. Our reported case highlights, that in rare incidents PUUV can cause hantavirus cardiopulmonary syndrome, a syndrome that is usually found after infections with New World hantaviruses, and neurological symptoms. Copyright © 2016 Elsevier B.V. All rights reserved.

Hantavirus Infection Prevalence in Wild Rodents and Human Anti-Hantavirus Serological Profiles from Different Geographic Areas of South Brazil

PubMed Central

Raboni, Sonia M.; Delfraro, Adriana; de Borba, Luana; Teixeira, Bernardo R.; Stella, Vanessa; de Araujo, Marina R.; Carstensen, Suzana; Rubio, Giselia; Maron, Angela; Lemos, Elba R. S.; D'Andrea, Paulo S.; Duarte dos Santos, Claudia N.

2012-01-01

Paraná state presents the fourth highest number of accumulated cases of hantavirus pulmonary syndrome in Brazil. To map the risk areas for hantavirus transmission we carried out a study based on rodent trapping and determined the anti-hantavirus seroprevalence in these animals and in the inhabitants of these localities. Overall seroprevalence in rodents and humans were 2.5% and 2.4%, respectively. Eighty-two percent of the seropositive rodents were genetically analyzed. Phylogenetic analyses revealed that hantaviruses from rodent samples cluster with Araucária (Juquitiba-like) or Jaborá hantavirus genotypes. The Jaborá strain was identified in Akodon serrensis and Akodon montensis, whereas the Araucária strain was detected in Oligoryzomys nigripes, Oxymycterus judex, A. montensis, and Akodon paranaensis, with the latter species being identified for the first time as a natural host. These findings expose the complex relationships between virus and reservoirs in Brazil, which could have an impact on hantavirus transmission dynamics in nature and human epidemiology. PMID:22855773

Hantavirus infection prevalence in wild rodents and human anti-hantavirus serological profiles from different geographic areas of South Brazil.

PubMed

Raboni, Sonia M; Delfraro, Adriana; de Borba, Luana; Teixeira, Bernardo R; Stella, Vanessa; de Araujo, Marina R; Carstensen, Suzana; Rubio, Giselia; Maron, Angela; Lemos, Elba R S; D'Andrea, Paulo S; Duarte dos Santos, Claudia N

2012-08-01

Paraná state presents the fourth highest number of accumulated cases of hantavirus pulmonary syndrome in Brazil. To map the risk areas for hantavirus transmission we carried out a study based on rodent trapping and determined the anti-hantavirus seroprevalence in these animals and in the inhabitants of these localities. Overall seroprevalence in rodents and humans were 2.5% and 2.4%, respectively. Eighty-two percent of the seropositive rodents were genetically analyzed. Phylogenetic analyses revealed that hantaviruses from rodent samples cluster with Araucária (Juquitiba-like) or Jaborá hantavirus genotypes. The Jaborá strain was identified in Akodon serrensis and Akodon montensis, whereas the Araucária strain was detected in Oligoryzomys nigripes, Oxymycterus judex, A. montensis, and Akodon paranaensis, with the latter species being identified for the first time as a natural host. These findings expose the complex relationships between virus and reservoirs in Brazil, which could have an impact on hantavirus transmission dynamics in nature and human epidemiology.

Signs and Symptoms for Hantavirus Pulmonary Syndrome (HPS)

MedlinePlus

... Pulmonary Syndrome: A guide for tourists, campers, and hikers Publications and Links Outbreaks Seoul Virus Preventing Seoul ... as the lungs fill with fluid. Is the Disease Fatal? Yes. HPS can be fatal. It has ...

Prediction of Pan-Specific B-Cell Epitopes From Nucleocapsid Protein of Hantaviruses Causing Hantavirus Cardiopulmonary Syndrome.

PubMed

Kalaiselvan, Sagadevan; Sankar, Sathish; Ramamurthy, Mageshbabu; Ghosh, Asit Ranjan; Nandagopal, Balaji; Sridharan, Gopalan

2017-08-01

Hantaviruses are emerging viral pathogens that causes hantavirus cardiopulmonary syndrome (HCPS) in the Americas, a severe, sometimes fatal, respiratory disease in humans with a case fatality rate of ≥50%. IgM and IgG-based serological detection methods are the most common approaches used for laboratory diagnosis of hantaviruses. Such emerging viral pathogens emphasizes the need for improved rapid diagnostic devices and vaccines incorporating pan-specific epitopes of genotypes. We predicted linear B-cell epitopes for hantaviruses that are specific to genotypes causing HCPS in humans using in silico prediction servers. We modeled the Andes and Sin Nombre hantavirus nucleocapsid protein to locate the identified epitopes. Based on the mean percent prediction probability score, epitope IMASKSVGS/TAEEKLKKKSAF was identified as the best candidate B-cell epitope specific for hantaviruses causing HCPS. Promiscuous epitopes were identified in the C-terminal of the protein. Our study for the first time has reported pan-specific B-cell epitopes for developing immunoassays in the detection of antibodies to hantaviruses causing HCPS. Identification of epitopes with pan-specific recognition of all genotypes causing HCPS could be valuable for the development of immunodiagnositic tools toward pan-detection of hantavirus antibodies in ELISA. J. Cell. Biochem. 118: 2320-2324, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

First evidence of asymptomatic infection related to the Araucaria (Juquitiba-like) hantavirus.

PubMed

de Borba, Luana; Delfraro, Adriana; Raboni, Sonia M; dos Santos, Claudia Nunes Duarte

2013-08-05

Hantavirus pulmonary syndrome (HPS) is a severe disease, transmitted to humans by inhalation of virus-contaminated aerosols from rodent excreta. Epidemiological, clinical and laboratory data confirmed a fatal HPS case and an asymptomatic infection in a household contact, both caused by Araucaria hantavirus, which has previously been found only in patients with HPS. This is the first report of asymptomatic infection related to a pathogenic hantavirus genotype, highlighting the need for additional studies on characterisation of viral and genetic mechanisms associated with this disease.

Complete Genome Sequence of a Novel Hantavirus Variant of Rio Mamoré Virus, Maripa Virus, from French Guiana

PubMed Central

Matheus, Séverine; Lavergne, Anne; de Thoisy, Benoît; Dussart, Philippe

2012-01-01

We report the first complete genome sequence of Maripa virus identified in 2009 from a patient with hantavirus pulmonary syndrome in French Guiana. Maripa virus corresponds to a new variant of the Rio Mamoré virus species in the Bunyaviridae family, genus Hantavirus. PMID:22492924

DNA vaccine-derived human IgG produced in transchromosomal bovines protect in lethal models of hantavirus pulmonary syndrome.

PubMed

Hooper, Jay W; Brocato, Rebecca L; Kwilas, Steven A; Hammerbeck, Christopher D; Josleyn, Matthew D; Royals, Michael; Ballantyne, John; Wu, Hua; Jiao, Jin-an; Matsushita, Hiroaki; Sullivan, Eddie J

2014-11-26

Polyclonal immunoglobulin-based medical products have been used successfully to treat diseases caused by viruses for more than a century. We demonstrate the use of DNA vaccine technology and transchromosomal bovines (TcBs) to produce fully human polyclonal immunoglobulins (IgG) with potent antiviral neutralizing activity. Specifically, two hantavirus DNA vaccines [Andes virus (ANDV) DNA vaccine and Sin Nombre virus (SNV) DNA vaccine] were used to produce a candidate immunoglobulin product for the prevention and treatment of hantavirus pulmonary syndrome (HPS). A needle-free jet injection device was used to vaccinate TcB, and high-titer neutralizing antibodies (titers >1000) against both viruses were produced within 1 month. Plasma collected at day 10 after the fourth vaccination was used to produce purified α-HPS TcB human IgG. Treatment with 20,000 neutralizing antibody units (NAU)/kg starting 5 days after challenge with ANDV protected seven of eight animals, whereas zero of eight animals treated with the same dose of normal TcB human IgG survived. Likewise, treatment with 20,000 NAU/kg starting 5 days after challenge with SNV protected immunocompromised hamsters from lethal HPS, protecting five of eight animals. Our findings that the α-HPS TcB human IgG is capable of protecting in animal models of lethal HPS when administered after exposure provides proof of concept that this approach can be used to develop candidate next-generation polyclonal immunoglobulin-based medical products without the need for human donors, despeciation protocols, or inactivated/attenuated vaccine antigen. Copyright © 2014, American Association for the Advancement of Science.

Genetic Diversity and Distribution of Peromyscus-Borne Hantaviruses in North America

PubMed Central

Monroe, Martha C.; Morzunov, Sergey P.; Johnson, Angela M.; Bowen, Michael D.; Artsob, Harvey; Yates, Terry; Peters, C.J.; Rollin, Pierre E.; Ksiazek, Thomas G.

1999-01-01

The 1993 outbreak of hantavirus pulmonary syndrome (HPS) in the southwestern United States was associated with Sin Nombre virus, a rodent-borne hantavirus; The virus' primary reservoir is the deer mouse (Peromyscus maniculatus). Hantavirus-infected rodents were identified in various regions of North America. An extensive nucleotide sequence database of an 139 bp fragment amplified from virus M genomic segments was generated. Phylogenetic analysis confirmed that SNV-like hantaviruses are widely distributed in Peromyscus species rodents throughout North America. Classic SNV is the major cause of HPS in North America, but other Peromyscine-borne hantaviruses, e.g., New York and Monongahela viruses, are also associated with HPS cases. Although genetically diverse, SNV-like viruses have slowly coevolved with their rodent hosts. We show that the genetic relationships of hantaviruses in the Americas are complex, most likely as a result of the rapid radiation and speciation of New World sigmodontine rodents and occasional virus-host switching events. PMID:10081674

T Cells and Pathogenesis of Hantavirus Cardiopulmonary Syndrome and Hemorrhagic Fever with Renal Syndrome

PubMed Central

Terajima, Masanori; Ennis, Francis A.

2011-01-01

We previously hypothesized that increased capillary permeability observed in both hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS) may be caused by hantavirus-specific cytotoxic T cells attacking endothelial cells presenting viral antigens on their surface based on clinical observations and in vitro experiments. In HCPS, hantavirus-specific T cell responses positively correlated with disease severity. In HFRS, in one report, contrary to HCPS, T cell responses negatively correlated with disease severity, but in another report the number of regulatory T cells, which are thought to suppress T cell responses, negatively correlated with disease severity. In rat experiments, in which hantavirus causes persistent infection, depletion of regulatory T cells helped infected rats clear virus without inducing immunopathology. These seemingly contradictory findings may suggest delicate balance in T cell responses between protection and immunopathogenesis. Both too strong and too weak T cell responses may lead to severe disease. It is important to clarify the role of T cells in these diseases for better treatment (whether to suppress T cell functions) and protection (vaccine design) which may need to take into account viral factors and the influence of HLA on T cell responses. PMID:21994770

T cells and pathogenesis of hantavirus cardiopulmonary syndrome and hemorrhagic fever with renal syndrome.

PubMed

Terajima, Masanori; Ennis, Francis A

2011-07-01

We previously hypothesized that increased capillary permeability observed in both hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS) may be caused by hantavirus-specific cytotoxic T cells attacking endothelial cells presenting viral antigens on their surface based on clinical observations and in vitro experiments. In HCPS, hantavirus-specific T cell responses positively correlated with disease severity. In HFRS, in one report, contrary to HCPS, T cell responses negatively correlated with disease severity, but in another report the number of regulatory T cells, which are thought to suppress T cell responses, negatively correlated with disease severity. In rat experiments, in which hantavirus causes persistent infection, depletion of regulatory T cells helped infected rats clear virus without inducing immunopathology. These seemingly contradictory findings may suggest delicate balance in T cell responses between protection and immunopathogenesis. Both too strong and too weak T cell responses may lead to severe disease. It is important to clarify the role of T cells in these diseases for better treatment (whether to suppress T cell functions) and protection (vaccine design) which may need to take into account viral factors and the influence of HLA on T cell responses.

Ecological study of hantavirus infection in wild rodents in an endemic area in Brazil.

PubMed

Oliveira, Renata Carvalho; Gentile, Rosana; Guterres, Alexandro; Fernandes, Jorlan; Teixeira, Bernardo Rodrigues; Vaz, Vanderson; Valdez, Fernanda Pedone; Vicente, Luciana Helena Bassan; da Costa-Neto, Sócrates Fraga; Bonvicino, Cibele; D'Andrea, Paulo Sergio; Lemos, Elba R S

2014-03-01

A 3-year ecological study of small mammals was carried out in an endemic area for hantavirus pulmonary syndrome in the state of Santa Catarina in Southern Brazil. A total of 994 rodents of 14 different species corresponding to the subfamilies of Sigmodontinae, Murinae, Eumysopinae, and Caviinae were captured during 2004-2006. Oligoryzomys nigripes and Akodon montensis were the most abundant species and showed a clear seasonal pattern with higher population sizes during the winter. Rodent population outbreaks, associated within bamboo mast seeding events, were detected predominantly in areas where hantavirus pulmonary syndrome cases were notified in the state. Antibody reactivity to Hantavirus was detected in five sigmodontine species: O. nigripes (39/435), A. montensis (15/318), Akodon paranaensis (4/37), Thaptomys nigrita (1/86) and Sooretamys angouya (1/12). The highest hantavirus antibody prevalence occurred during the period of highest population size in A. montensis. For O. nigripes, hantavirus prevalence was higher in late spring, when reproduction was more frequent. Co-circulation of Juquitiba (JUQV) and Jabora (JABV) viruses was observed - JABV in A. paranaensis and A. montensis; JUQV in O. nigripes and T. nigrita. JABV occurrence was associated to gender and population size of the rodent while JUQV was related to gender, season, temperature, and locality. Copyright © 2013 Elsevier B.V. All rights reserved.

Cytokine expression during early and late phase of acute Puumala hantavirus infection

PubMed Central

2011-01-01

Background Hantaviruses of the family Bunyaviridae are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. An immune-mediated pathogenesis is discussed for both syndromes. The aim of our study was to investigate cytokine expression during the course of acute Puumala hantavirus infection. Results We retrospectively studied 64 patients hospitalised with acute Puumala hantavirus infection in 2010 during a hantavirus epidemic in Germany. Hantavirus infection was confirmed by positive anti-hantavirus IgG/IgM. Cytokine expression of IL-2, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α and TGF-β1 was analysed by ELISA during the early and late phase of acute hantavirus infection (average 6 and 12 days after onset of symptoms, respectively). A detailed description of the demographic and clinical presentation of severe hantavirus infection requiring hospitalization during the 2010 hantavirus epidemic in Germany is given. Acute hantavirus infection was characterized by significantly elevated levels of IL-2, IL-6, IL-8, TGF-β1 and TNF-α in both early and late phase compared to healthy controls. From early to late phase of disease, IL-6, IL-10 and TNF-α significantly decreased whereas TGF-β1 levels increased. Disease severity characterized by elevated creatinine and low platelet counts was correlated with high pro-inflammatory IL-6 and TNF-α but low immunosuppressive TGF-β1 levels and vice versa . Conclusion High expression of cytokines activating T-lymphocytes, monocytes and macrophages in the early phase of disease supports the hypothesis of an immune-mediated pathogenesis. In the late phase of disease, immunosuppressive TGF-β1 level increase significantly. We suggest that delayed induction of a protective immune mechanism to downregulate a massive early pro-inflammatory immune response might contribute to the pathologies characteristic of human hantavirus infection

Hantavirus Reservoirs: Current Status with an Emphasis on Data from Brazil

PubMed Central

Carvalho de Oliveira, Renata; Guterres, Alexandro; Fernandes, Jorlan; D’Andrea, Paulo Sérgio; Bonvicino, Cibele Rodrigues; de Lemos, Elba Regina Sampaio

2014-01-01

Since the recognition of hantavirus as the agent responsible for haemorrhagic fever in Eurasia in the 1970s and, 20 years later, the descovery of hantavirus pulmonary syndrome in the Americas, the genus Hantavirus has been continually described throughout the World in a variety of wild animals. The diversity of wild animals infected with hantaviruses has only recently come into focus as a result of expanded wildlife studies. The known reservoirs are more than 80, belonging to 51 species of rodents, 7 bats (order Chiroptera) and 20 shrews and moles (order Soricomorpha). More than 80genetically related viruses have been classified within Hantavirus genus; 25 recognized as human pathogens responsible for a large spectrum of diseases in the Old and New World. In Brazil, where the diversity of mammals and especially rodents is considered one of the largest in the world, 9 hantavirus genotypes have been identified in 12 rodent species belonging to the genus Akodon, Calomys, Holochilus, Oligoryzomys, Oxymycterus, Necromys and Rattus. Considering the increasing number of animals that have been implicated as reservoirs of different hantaviruses, the understanding of this diversity is important for evaluating the risk of distinct hantavirus species as human pathogens. PMID:24784571

Another case of "European hantavirus pulmonary syndrome" with severe lung, prior to kidney, involvement, and diagnosed by viral inclusions in lung macrophages.

PubMed

Gizzi, M; Delaere, B; Weynand, B; Clement, J; Maes, P; Vergote, V; Laenen, L; Hjelle, B; Verroken, A; Dive, A; Michaux, I; Evrard, P; Creytens, D; Bulpa, P

2013-10-01

Puumala virus (PUUV) is considered a classic Old World etiologic agent of nephropathia epidemica (NE), or hemorrhagic fever with renal syndrome (HFRS). HFRS is considered to be distinct from hantavirus (cardio-)pulmonary syndrome (HPS or HCPS), described in the New World. Here, we report a severe case, which fulfilled most, if not all, Centers for Disease Control and Prevention (CDC) criteria for HPS, needing non-invasive ventilation and subsequent acute hemodialysis. However, the etiological agent was PUUV, as proved by serological testing, real-time polymerase chain reaction (PCR), and sequencing. Viral antigen was detected by specific anti-PUUV immunostaining, showing, for the first time, greenish intracytoplasmic inclusions in bronchoalveolar lavage (BAL) macrophages. This case definitely confirms that HPS can be encountered during PUUV infections. Interestingly, special findings could render the diagnosis easier, such as greenish homogeneous cytoplasmic inclusions, surrounded by a fine clear halo in BAL macrophages. Therefore, although the diagnosis remains difficult before the onset of renal involvement, the occurrence of severe respiratory failure mimicking community-acquired pneumonia must alert the clinician for possible HPS, especially in endemic areas.

Andes Virus and First Case Report of Bermejo Virus Causing Fatal Pulmonary Syndrome

PubMed Central

Della Valle, Marcelo González; Alai, María Garcia; Cortada, Pedro; Villagra, Mario; Gianella, Alberto

2002-01-01

Two suspected hantavirus pulmonary syndrome (HPS) cases from Bolivia were confirmed by enzyme-linked immunosorbent assay. (ELISA)-ANDES was performed using N-Andes recombinant antigen serology in May and July 2000. Clot RNAs from the two patients were subjected to reverse transcription–polymerase chain reaction (PCR) amplification and sequencing. We describe two characterized cases of HPS. One was caused by infection with Bermejo virus and the other with Andes Nort viral lineage, both previously obtained from Oligoryzomys species. This is the first report of molecular identification of a human hantavirus associated with Bermejo virus. PMID:11971782

Hantavirus infection: a global zoonotic challenge.

PubMed

Jiang, Hong; Zheng, Xuyang; Wang, Limei; Du, Hong; Wang, Pingzhong; Bai, Xuefan

2017-02-01

Hantaviruses are comprised of tri-segmented negative sense single-stranded RNA, and are members of the Bunyaviridae family. Hantaviruses are distributed worldwide and are important zoonotic pathogens that can have severe adverse effects in humans. They are naturally maintained in specific reservoir hosts without inducing symptomatic infection. In humans, however, hantaviruses often cause two acute febrile diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). In this paper, we review the epidemiology and epizootiology of hantavirus infections worldwide.

Population Ecology of Hantavirus Rodent Hosts in Southern Brazil

PubMed Central

Teixeira, Bernardo R.; Loureiro, Nathalie; Strecht, Liana; Gentile, Rosana; Oliveira, Renata C.; Guterres, Alexandro; Fernandes, Jorlan; Mattos, Luciana H. B. V.; Raboni, Sonia M.; Rubio, Giselia; Bonvicino, Cibele R.; Duarte dos Santos, Claudia N.; Lemos, Elba R. S.; D'Andrea, Paulo S.

2014-01-01

In this study we analyze population dynamics of hantavirus rodent hosts and prevalence of infection over a 2-year period in Southern Brazil, a region with a high incidence of hantavirus pulmonary syndrome. The 14 small mammal species captured were composed of 10 rodents and four marsupials, the six most abundant species being Akodon serrensis, Oxymycterus judex, Akodon montensis, Akodon paranaensis, Oligoryzomys nigripes, and Thaptomys nigrita. These species displayed a similar pattern with increasing population sizes in fall/winter caused by recruitment and both, increase in reproductive activity and higher hantavirus prevalence in spring/summer. Specific associations between A. montensis/Jaborá Virus (JABV) and O. nigripes/Juquitiba-like Virus (JUQV-like) and spillover infections between A. paranaensis/JABV, A. serrensis/JABV, and A. paranaensis/JUQV-like were observed. Spillover infection in secondary hosts seems to play an important role in maintaining JABV and JUQV-like in the hantavirus sylvatic cycle mainly during periods of low prevalence in primary hosts. PMID:24935954

Ribavirin protects Syrian hamsters against lethal hantavirus pulmonary syndrome--after intranasal exposure to Andes virus.

PubMed

Ogg, Monica; Jonsson, Colleen B; Camp, Jeremy V; Hooper, Jay W

2013-11-08

Andes virus, ANDV, harbored by wild rodents, causes the highly lethal hantavirus pulmonary syndrome (HPS) upon transmission to humans resulting in death in 30% to 50% of the cases. As there is no treatment for this disease, we systematically tested the efficacy of ribavirin in vitro and in an animal model. In vitro assays confirmed antiviral activity and determined that the most effective doses were 40 µg/mL and above. We tested three different concentrations of ribavirin for their capability to prevent HPS in the ANDV hamster model following an intranasal challenge. While the highest level of ribavirin (200 mg/kg) was toxic to the hamster, both the middle (100 mg/kg) and the lowest concentration (50 mg/kg) prevented HPS in hamsters without toxicity. Specifically, 8 of 8 hamsters survived intranasal challenge for both of those groups whereas 7 of 8 PBS control-treated animals developed lethal HPS. Further, we report that administration of ribavirin at 50 mg/kg/day starting on days 6, 8, 10, or 12 post-infection resulted in significant protection against HPS in all groups. Administration of ribavirin at 14 days post-infection also provided a significant level of protection against lethal HPS. These data provide in vivo evidence supporting the potential use of ribavirin as a post-exposure treatment to prevent HPS after exposure by the respiratory route.

DNA vaccine-generated duck polyclonal antibodies as a postexposure prophylactic to prevent hantavirus pulmonary syndrome (HPS).

PubMed

Brocato, Rebecca; Josleyn, Matthew; Ballantyne, John; Vial, Pablo; Hooper, Jay W

2012-01-01

Andes virus (ANDV) is the predominant cause of hantavirus pulmonary syndrome (HPS) in South America and the only hantavirus known to be transmitted person-to-person. There are no vaccines, prophylactics, or therapeutics to prevent or treat this highly pathogenic disease (case-fatality 35-40%). Infection of Syrian hamsters with ANDV results in a disease that closely mimics human HPS in incubation time, symptoms of respiratory distress, and disease pathology. Here, we evaluated the feasibility of two postexposure prophylaxis strategies in the ANDV/hamster lethal disease model. First, we evaluated a natural product, human polyclonal antibody, obtained as fresh frozen plasma (FFP) from a HPS survivor. Second, we used DNA vaccine technology to manufacture a polyclonal immunoglobulin-based product that could be purified from the eggs of vaccinated ducks (Anas platyrhynchos). The natural "despeciation" of the duck IgY (i.e., Fc removed) results in an immunoglobulin predicted to be minimally reactogenic in humans. Administration of ≥ 5,000 neutralizing antibody units (NAU)/kg of FFP-protected hamsters from lethal disease when given up to 8 days after intranasal ANDV challenge. IgY/IgYΔFc antibodies purified from the eggs of DNA-vaccinated ducks effectively neutralized ANDV in vitro as measured by plaque reduction neutralization tests (PRNT). Administration of 12,000 NAU/kg of duck egg-derived IgY/IgYΔFc protected hamsters when administered up to 8 days after intranasal challenge and 5 days after intramuscular challenge. These experiments demonstrate that convalescent FFP shows promise as a postexposure HPS prophylactic. Moreover, these data demonstrate the feasibility of using DNA vaccine technology coupled with the duck/egg system to manufacture a product that could supplement or replace FFP. The DNA vaccine-duck/egg system can be scaled as needed and obviates the necessity of using limited blood products obtained from a small number of HPS survivors. This is the

A Global Perspective on Hantavirus Ecology, Epidemiology, and Disease

PubMed Central

Jonsson, Colleen B.; Figueiredo, Luiz Tadeu Moraes; Vapalahti, Olli

2010-01-01

Summary: Hantaviruses are enzootic viruses that maintain persistent infections in their rodent hosts without apparent disease symptoms. The spillover of these viruses to humans can lead to one of two serious illnesses, hantavirus pulmonary syndrome and hemorrhagic fever with renal syndrome. In recent years, there has been an improved understanding of the epidemiology, pathogenesis, and natural history of these viruses following an increase in the number of outbreaks in the Americas. In this review, current concepts regarding the ecology of and disease associated with these serious human pathogens are presented. Priorities for future research suggest an integration of the ecology and evolution of these and other host-virus ecosystems through modeling and hypothesis-driven research with the risk of emergence, host switching/spillover, and disease transmission to humans. PMID:20375360

[Epidemiology of hantaviruses in Baden-Wurttemberg].

PubMed

Kimmig, P; Silva-González, R; Backe, H; Brockmann, S; Oehme, R; Ernst, E; Mackenstedt, U

2001-02-01

Hantavirus, originally named after the Hantaan River in Korea, is the aetiologic agent for the Hemorrhagic Fever with Renal Syndrome (HFRS) in the asian region, in the Americas for the Hantavirus Pulmonary Syndrome (HPS). In Middle Europe hantaviruses are responsible for the "Nephropathia Epidemica" (NE), a mild form of HFRS. Hantaviruses belong to the family of Bunyaviridae. Like other members of this family their genome consists of three segments of single stranded RNA (ss-RNA) leading to various subtypes, strongly associated with different rodent hosts. There are two major groups, the hantaan lineage harbored by murine rodents and the Puumala lineage harbored by arvicolidae ("old world") and sigmodontidae ("new world"). Infected rodents may develop chronic infections for months or even life-long and may shed infectious virus with urine and feces. The primary mode of infection of man occurs by inhaling contaminated aerosols or soil particles. The collection of epidemiologic data in the state of Baden-Württemberg was realized in three different steps: Collection and localisation of clinical cases (n = 62): A concentration of clinical cases in the middle of the state was found. The examination of the seroprevalence of exposed persons: By the examination of 4000 sera from forest workers, a seroprevalence with an average of 2.1% was found. In the districts of Reutlingen and Tübingen seroprevalences up to 9% were found. This leads to the assumption that there are endemic areas. Epidemiologic studies of reservoir hosts: Serologic surveys of rodents (n = 1150) in the described areas yielded to a seroprevalence up to 10-30%. Virus carriers were determined with RT-PCR and nested-PCR testing. The prevalence in the rodent population showed an average of 10%. The isolated subtypes were all identified as members of the Puumala-lineage. The origin of sporadic infections with Hantavirus of the Hantaan-lineage in Baden-Wuerttemberg is still unknown.

Geographic Distribution of Hantaviruses Associated with Neotomine and Sigmodontine Rodents, Mexico

PubMed Central

Milazzo, Mary L.; Cajimat, Maria N.B.; Romo, Hannah E.; Estrada-Franco, Jose G.; Iñiguez-Dávalos, L. Ignacio; Bradley, Robert D.

2012-01-01

To increase our knowledge of the geographic distribution of hantaviruses associated with neotomine or sigmodontine rodents in Mexico, we tested 876 cricetid rodents captured in 18 Mexican states (representing at least 44 species in the subfamily Neotominae and 10 species in the subfamily Sigmodontinae) for anti-hantavirus IgG. We found antibodies against hantavirus in 35 (4.0%) rodents. Nucleotide sequence data from 5 antibody-positive rodents indicated that Sin Nombre virus (the major cause of hantavirus pulmonary syndrome [HPS] in the United States) is enzootic in the Mexican states of Nuevo León, San Luis Potosí, Tamaulipas, and Veracruz. However, HPS has not been reported from these states, which suggests that in northeastern Mexico, HPS has been confused with other rapidly progressive, life-threatening respiratory diseases. Analyses of nucleotide sequence data from 19 other antibody-positive rodents indicated that El Moro Canyon virus and Limestone Canyon virus are geographically widely distributed in Mexico. PMID:22469569

Fugong virus, a novel hantavirus harbored by the small oriental vole (Eothenomys eleusis) in China.

PubMed

Ge, Xing-Yi; Yang, Wei-Hong; Pan, Hong; Zhou, Ji-Hua; Han, Xi; Zhu, Guang-Jian; Desmond, James S; Daszak, Peter; Shi, Zheng-Li; Zhang, Yun-Zhi

2016-02-16

Rodents are natural reservoirs of hantaviruses, which cause two disease types: hemorrhagic fever with renal syndrome in Eurasia and hantavirus pulmonary syndrome in North America. Hantaviruses related human cases have been observed throughout Asia, Europe, Africa, and North America. To date, 23 distinct species of hantaviruses, hosted by reservoir, have been identified. However, the diversity and number of hantaviruses are likely underestimated in China, and hantavirus species that cause disease in many regions, including Yunnan province, are unknown. In August 2012, we collected tissue samples from 189 captured animals, including 15 species belonging to 10 genera, 5 families, and 4 orders in Fugong county, Yunnan province, China. Seven species were positive for hantavirus: Eothenomys eleusis (42/94), Apodemus peninsulae (3/25), Niviventer eha (3/27), Cryptotis montivaga (2/8), Anourosorex squamipes (1/1), Sorex araneus (1/1), and Mustela sibirica (1/2). We characterized one full-length genomic sequence of the virus (named fugong virus, FUGV) from a small oriental vole (Eothenomys eleusis). The full-length sequences of the small, medium, and large segments of FUGV were 1813, 3630, and 6531 nt, respectively. FUGV was most closely related to hantavirus LX309, a previously reported species detected in the red-backed vole in Luxi county, Yunnan province, China. However, the amino acid sequences of nucleocapsid (N), glycoprotein (G), and large protein (L) were highly divergent from those of Hantavirus LX309, with amino acid differences of 11.2, 15.3, and 12.7 %, respectively. In phylogenetic trees, FUGV clustered in the lineage corresponding to hantaviruses carried by rodents in the subfamily Arvicolinae. High prevalence of hantavirus infection in small mammals was found in Fugong county, Yunnan province, China. A novel hantavirus species FUGV was identified from the small oriental vole. This virus is phylogenetic clustering with another hantavirus LX309, but shows

Pneumonitis in Syrian golden hamsters (Mesocricetus auratus) infected with Río Mamoré virus (family Bunyaviridae, genus Hantavirus)

PubMed Central

Milazzo, Mary Louise; Eyzaguirre, Eduardo J.; Fulhorst, Charles F.

2014-01-01

Rio Mamoré virus is an etiological agent of hantavirus pulmonary syndrome in South America. The purpose of this study was to determine whether Rio Mamoré virus strain HTN-007 in Syrian golden hamsters is pathogenic. None of 37 adult hamsters infected by intramuscular injection of HTN-007, including 10 animals killed on Day 42 or 43 post-inoculation, exhibited any symptom of disease. Histological abnormalities included severe or moderately severe pneumonitis in 6 (46.2%) of the 13 animals killed on Day 7 or 10 post-inoculation. The primary target of infection in lung was the endothelium of the microvasculature. Collectively, these results indicate that Rio Mamoré virus strain HTN-007 in adult Syrian golden hamsters can cause a nonlethal disease that is pathologically similar to hantavirus pulmonary syndrome. PMID:25064267

Preferential host switching and its relation with Hantavirus diversification in South America.

PubMed

Rivera, Paula C; González-Ittig, Raul E; Gardenal, Cristina N

2015-09-01

In recent years, the notion of co-speciation between Hantavirus species and their hosts was discarded in favour of a more likely explanation: preferential host switching. However, the relative importance of this last process in shaping the evolutionary history of hantaviruses remains uncertain, given the present limited knowledge not only of virus-host relationships but also of the pathogen and reservoir phylogenies. In South America, more than 25 hantavirus genotypes were detected; several of them act as aetiological agents of hantavirus pulmonary syndrome (HPS). An understanding of the diversity of hantaviruses and of the processes underlying host switching is critical since human cases of HPS are almost exclusively the result of human-host interactions. In this study, we tested if preferential host switching is the main process driving hantavirus diversification in South America, by performing a co-phylogenetic analysis of the viruses and their primary hosts. We also suggest a new level of amino acid divergence to define virus species in the group. Our results indicate that preferential host switching would not be the main process driving virus diversification. The historical geographical proximity among rodent hosts emerges as an alternative hypothesis to be tested.

Hantavirus pulmonary syndrome, Southern Chile, 1995-2012.

PubMed

Riquelme, Raúl; Rioseco, María Luisa; Bastidas, Lorena; Trincado, Daniela; Riquelme, Mauricio; Loyola, Hugo; Valdivieso, Francisca

2015-04-01

Hantavirus is endemic to the Region de Los Lagos in southern Chile; its incidence is 8.5 times higher in the communes of the Andean area than in the rest of the region. We analyzed the epidemiologic aspects of the 103 cases diagnosed by serology and the clinical aspects of 80 hospitalized patients during 1995-2012. Cases in this region clearly predominated during winter, whereas in the rest of the country, they occur mostly during summer. Mild, moderate, and severe disease was observed, and the case-fatality rate was 32%. Shock caused death in 75% of those cases; high respiratory frequency and elevated creatinine plasma level were independent factors associated with death. Early clinical suspicion, especially in rural areas, should prompt urgent transfer to a hospital with an intensive care unit and might help decrease the high case-fatality rate.

Maporal Hantavirus Causes Mild Pathology in Deer Mice (Peromyscus maniculatus).

PubMed

McGuire, Amanda; Miedema, Kaitlyn; Fauver, Joseph R; Rico, Amber; Aboellail, Tawfik; Quackenbush, Sandra L; Hawkinson, Ann; Schountz, Tony

2016-10-18

Rodent-borne hantaviruses can cause two human diseases with many pathological similarities: hantavirus cardiopulmonary syndrome (HCPS) in the western hemisphere and hemorrhagic fever with renal syndrome in the eastern hemisphere. Each virus is hosted by specific reservoir species without conspicuous disease. HCPS-causing hantaviruses require animal biosafety level-4 (ABSL-4) containment, which substantially limits experimental research of interactions between the viruses and their reservoir hosts. Maporal virus (MAPV) is a South American hantavirus not known to cause disease in humans, thus it can be manipulated under ABSL-3 conditions. The aim of this study was to develop an ABSL-3 hantavirus infection model using the deer mouse ( Peromyscus maniculatus ), the natural reservoir host of Sin Nombre virus (SNV), and a virus that is pathogenic in another animal model to examine immune response of a reservoir host species. Deer mice were inoculated with MAPV, and viral RNA was detected in several organs of all deer mice during the 56 day experiment. Infected animals generated both nucleocapsid-specific and neutralizing antibodies. Histopathological lesions were minimal to mild with the peak of the lesions detected at 7-14 days postinfection, mainly in the lungs, heart, and liver. Low to modest levels of cytokine gene expression were detected in spleens and lungs of infected deer mice, and deer mouse primary pulmonary cells generated with endothelial cell growth factors were susceptible to MAPV with viral RNA accumulating in the cellular fraction compared to infected Vero cells. Most features resembled that of SNV infection of deer mice, suggesting this model may be an ABSL-3 surrogate for studying the host response of a New World hantavirus reservoir.

Differential Regulation of PAI-1 in Hantavirus Cardiopulmonary Syndrome and Hemorrhagic Fever With Renal Syndrome.

PubMed

Bellomo, Carla; Korva, Miša; Papa, Anna; Mäkelä, Satu; Mustonen, Jukka; Avšič-Županc, Tatjana; Vaheri, Antti; Martinez, Valeria P; Strandin, Tomas

2018-02-01

We analyzed the levels of circulating tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI)-1 in acute hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS). The levels of tPA commonly increased in both diseases, whereas PAI-1 correlated with disease severity in HCPS but not in HFRS.

Hantavirus infections among overnight visitors to Yosemite National Park, California, USA, 2012.

PubMed

Núñez, Jonathan J; Fritz, Curtis L; Knust, Barbara; Buttke, Danielle; Enge, Barryett; Novak, Mark G; Kramer, Vicki; Osadebe, Lynda; Messenger, Sharon; Albariño, César G; Ströher, Ute; Niemela, Michael; Amman, Brian R; Wong, David; Manning, Craig R; Nichol, Stuart T; Rollin, Pierre E; Xia, Dongxiang; Watt, James P; Vugia, Duc J

2014-03-01

In summer 2012, an outbreak of hantavirus infections occurred among overnight visitors to Yosemite National Park in California, USA. An investigation encompassing clinical, epidemiologic, laboratory, and environmental factors identified 10 cases among residents of 3 states. Eight case-patients experienced hantavirus pulmonary syndrome, of whom 5 required intensive care with ventilatory support and 3 died. Staying overnight in a signature tent cabin (9 case-patients) was significantly associated with becoming infected with hantavirus (p<0.001). Rodent nests and tunnels were observed in the foam insulation of the cabin walls. Rodent trapping in the implicated area resulted in high trap success rate (51%), and antibodies reactive to Sin Nombre virus were detected in 10 (14%) of 73 captured deer mice. All signature tent cabins were closed and subsequently dismantled. Continuous public awareness and rodent control and exclusion are key measures in minimizing the risk for hantavirus infection in areas inhabited by deer mice.

Hantavirus Infections among Overnight Visitors to Yosemite National Park, California, USA, 2012

PubMed Central

Núñez, Jonathan J.; Fritz, Curtis L.; Knust, Barbara; Buttke, Danielle; Enge, Barryett; Novak, Mark G.; Kramer, Vicki; Osadebe, Lynda; Messenger, Sharon; Albariño, César G.; Ströher, Ute; Niemela, Michael; Amman, Brian R.; Wong, David; Manning, Craig R.; Nichol, Stuart T.; Rollin, Pierre E.; Xia, Dongxiang; Watt, James P.

2014-01-01

In summer 2012, an outbreak of hantavirus infections occurred among overnight visitors to Yosemite National Park in California, USA. An investigation encompassing clinical, epidemiologic, laboratory, and environmental factors identified 10 cases among residents of 3 states. Eight case-patients experienced hantavirus pulmonary syndrome, of whom 5 required intensive care with ventilatory support and 3 died. Staying overnight in a signature tent cabin (9 case-patients) was significantly associated with becoming infected with hantavirus (p<0.001). Rodent nests and tunnels were observed in the foam insulation of the cabin walls. Rodent trapping in the implicated area resulted in high trap success rate (51%), and antibodies reactive to Sin Nombre virus were detected in 10 (14%) of 73 captured deer mice. All signature tent cabins were closed and subsequently dismantled. Continuous public awareness and rodent control and exclusion are key measures in minimizing the risk for hantavirus infection in areas inhabited by deer mice. PMID:24565589

Pneumonitis in Syrian golden hamsters (Mesocricetus auratus) infected with Rio Mamoré virus (family Bunyaviridae, genus Hantavirus).

PubMed

Milazzo, Mary Louise; Eyzaguirre, Eduardo J; Fulhorst, Charles F

2014-10-13

Rio Mamoré virus is an etiological agent of hantavirus pulmonary syndrome in South America. The purpose of this study was to determine whether Rio Mamoré virus strain HTN-007 in Syrian golden hamsters is pathogenic. None of 37 adult hamsters infected by intramuscular injection of HTN-007, including 10 animals killed on Day 42 or 43 post-inoculation, exhibited any symptom of disease. Histological abnormalities included severe or moderately severe pneumonitis in 6 (46.2%) of the 13 animals killed on Day 7 or 10 post-inoculation. The primary target of infection in lung was the endothelium of the microvasculature. Collectively, these results indicate that Rio Mamoré virus strain HTN-007 in adult Syrian golden hamsters can cause a nonlethal disease that is pathologically similar to hantavirus pulmonary syndrome. Copyright © 2014 Elsevier B.V. All rights reserved.

Rapid, whole blood diagnostic test for detecting anti-hantavirus antibody in rats.

PubMed

Amada, Takako; Yoshimatsu, Kumiko; Yasuda, Shumpei P; Shimizu, Kenta; Koma, Takaaki; Hayashimoto, Nobuhito; Gamage, Chandika D; Nishio, Sanae; Takakura, Akira; Arikawa, Jiro

2013-10-01

Hantavirus is a causative agent of rodent-borne viral zoonoses, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome. Seoul virus (SEOV) is a causative agent of urban and laboratory rat-associated HFRS worldwide. Surveillance of rodents has been done mainly by serological detection of hantavirus-specific antibodies by enzyme linked immunosorbent assay (ELISA) and immunofluorescent antibody assay (IFA). An immunochromatographic (ICG) test was developed with the N-terminal 103 amino acids of nucleocapsid protein of Hantaan virus expressed by Escherichia coli as an antigen to detect IgG antibody specific to hantavirus in sera from Rattus sp. animals. Antibody-detecting sensitivity of the ICG test was the same as that of ELISA and about 100-times higher than that of IFA. Overall sensitivities and specificities of the ICG test in comparison to ELISA and IFA for sera from 192 urban rats and 123 laboratory rats were 99.3% and 100%, respectively. Diluted whole blood samples without separation could be used for the ICG test. The ICG test enabled detection of antibodies to SEOV, Hantaan, Dobrava/Belgrade, and Thailand viruses, which are causative agents of HFRS throughout Eurasia. The ICG test is a rapid, simple and safe method for diagnosis of SEOV infection in rats. Copyright © 2013 Elsevier B.V. All rights reserved.

Andes Virus M Genome Segment is Not Sufficient to Confer the Virulence Associated With Andres Virus in Syrian Hamsters

DTIC Science & Technology

2004-01-01

Hantavirus ; Reassortant; Hantavirus pulmonary syndrome ; HamsterIntroduction Hantaviruses are members of the Bunyaviridae...Andes virus (ANDV), members of the genus Hantavirus , in the family Bunyaviridae, are causative agents of hantavirus pulmonary syndrome (HPS) in North and...in humans: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) (Lee et al., 1982; Nichol et al., 1993). Almost

Gene Gun-Delivered DNA Vaccines for Hemorrhagic Fever With Renal Syndrome: Advancement to Clinical Trials

DTIC Science & Technology

2008-12-01

bioterrorism pathogens that threaten troops. 1. INTRODUCTION Hantaviruses are RNA viruses belonging to the family Bunyaviridae, and are...the etiologic agents of hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome in the New World. The...viruses are carried by persistently infected rodents and are found worldwide. There are no licensed vaccines for hantaviruses ; thus, they continue to

NK Cell Activation in Human Hantavirus Infection Explained by Virus-Induced IL-15/IL15Rα Expression

PubMed Central

Braun, Monika; Björkström, Niklas K.; Gupta, Shawon; Sundström, Karin; Ahlm, Clas; Klingström, Jonas; Ljunggren, Hans-Gustaf

2014-01-01

Clinical infection with hantaviruses cause two severe acute diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). These diseases are characterized by strong immune activation, increased vascular permeability, and up to 50% case-fatality rates. One prominent feature observed in clinical hantavirus infection is rapid expansion of natural killer (NK) cells in peripheral blood of affected individuals. We here describe an unusually high state of activation of such expanding NK cells in the acute phase of clinical Puumala hantavirus infection. Expanding NK cells expressed markedly increased levels of activating NK cell receptors and cytotoxic effector molecules. In search for possible mechanisms behind this NK cell activation, we observed virus-induced IL-15 and IL-15Rα on infected endothelial and epithelial cells. Hantavirus-infected cells were shown to strongly activate NK cells in a cell-cell contact-dependent way, and this response was blocked with anti-IL-15 antibodies. Surprisingly, the strength of the IL-15-dependent NK cell response was such that it led to killing of uninfected endothelial cells despite expression of normal levels of HLA class I. In contrast, hantavirus-infected cells were resistant to NK cell lysis, due to a combination of virus-induced increase in HLA class I expression levels and hantavirus-mediated inhibition of apoptosis induction. In summary, we here describe a possible mechanism explaining the massive NK cell activation and proliferation observed in HFRS patients caused by Puumala hantavirus infection. The results add further insights into mechanisms behind the immunopathogenesis of hantavirus infections in humans and identify new possible targets for intervention. PMID:25412359

Hantavirus Pulmonary Syndrome , Southern Chile, 1995–2012

PubMed Central

Riquelme, Raúl; Rioseco, María Luisa; Bastidas, Lorena; Trincado, Daniela; Riquelme, Mauricio; Loyola, Hugo; Valdivieso, Francisca

2015-01-01

Hantavirus is endemic to the Region de Los Lagos in southern Chile; its incidence is 8.5 times higher in the communes of the Andean area than in the rest of the region. We analyzed the epidemiologic aspects of the 103 cases diagnosed by serology and the clinical aspects of 80 hospitalized patients during 1995–2012. Cases in this region clearly predominated during winter, whereas in the rest of the country, they occur mostly during summer. Mild, moderate, and severe disease was observed, and the case-fatality rate was 32%. Shock caused death in 75% of those cases; high respiratory frequency and elevated creatinine plasma level were independent factors associated with death. Early clinical suspicion, especially in rural areas, should prompt urgent transfer to a hospital with an intensive care unit and might help decrease the high case-fatality rate. PMID:25816116

Serologic survey on hantavirus in blood donors from the state of Santa Catarina, Brazil.

PubMed

Cordova, Caio Maurício Mendes de; Figueiredo, Luiz Tadeu Moraes

2014-01-01

Emergent diseases such as Hantavirus Cardio-pulmonary Syndrome (HCPS) are able to create a significant impact on human populations due to their seriousness and high fatality rate. Santa Catarina, located in the South of Brazil, is the leading state for HCPS with 267 reported cases from 1999 to 2011. We present here a serological survey on hantavirus in blood donors from different cities of the state of Santa Catarina, with an IgG-ELISA using a recombinant nucleocapsid protein from Araraquara hantavirus as an antigen. In total, 314 donors from blood banks participated in the study, geographically covering the whole state. Among these, 14 individuals (4.4%) had antibodies to hantavirus: four of 50 (8% positivity) from Blumenau, four of 52 (7.6%) from Joinville, three of 50 (6%) from Florianópolis, two of 50 (4%) from Chapecó and one of 35 (2.8%) from Joaçaba. It is possible that hantaviruses are circulating across almost the whole state, with important epidemiological implications. Considering that the seropositive blood donors are healthy individuals, it is possible that hantaviruses may be causing unrecognized infections, which are either asymptomatic or clinically nonspecific, in addition to HCPS. It is also possible that more than one hantavirus type could be circulating in this region, causing mostly benign infections.

Endothelial Cell Permeability during Hantavirus Infection Involves Factor XII-Dependent Increased Activation of the Kallikrein-Kinin System

PubMed Central

Taylor, Shannon L.; Wahl-Jensen, Victoria; Copeland, Anna Maria; Jahrling, Peter B.; Schmaljohn, Connie S.

2013-01-01

Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) are diseases caused by hantavirus infections and are characterized by vascular leakage due to alterations of the endothelial barrier. Hantavirus-infected endothelial cells (EC) display no overt cytopathology; consequently, pathogenesis models have focused either on the influx of immune cells and release of cytokines or on increased degradation of the adherens junction protein, vascular endothelial (VE)-cadherin, due to hantavirus-mediated hypersensitization of EC to vascular endothelial growth factor (VEGF). To examine endothelial leakage in a relevant in vitro system, we co-cultured endothelial and vascular smooth muscle cells (vSMC) to generate capillary blood vessel-like structures. In contrast to results obtained in monolayers of cultured EC, we found that despite viral replication in both cell types as well as the presence of VEGF, infected in vitro vessels neither lost integrity nor displayed evidence of VE-cadherin degradation. Here, we present evidence for a novel mechanism of hantavirus-induced vascular leakage involving activation of the plasma kallikrein-kinin system (KKS). We show that incubation of factor XII (FXII), prekallikrein (PK), and high molecular weight kininogen (HK) plasma proteins with hantavirus-infected EC results in increased cleavage of HK, higher enzymatic activities of FXIIa/kallikrein (KAL) and increased liberation of bradykinin (BK). Measuring cell permeability in real-time using electric cell-substrate impedance sensing (ECIS), we identified dramatic increases in endothelial cell permeability after KKS activation and liberation of BK. Furthermore, the alterations in permeability could be prevented using inhibitors that directly block BK binding, the activity of FXIIa, or the activity of KAL. Lastly, FXII binding and autoactivation is increased on the surface of hantavirus-infected EC. These data are the first to demonstrate KKS activation during

'Bedside assessment' of acute hantavirus infections and their possible classification into the spectrum of haemophagocytic syndromes.

PubMed

Clement, J; Colson, P; Saegeman, V; Lagrou, K; Van Ranst, M

2016-07-01

Hantavirus infections, recently renamed 'hantavirus fever' (HTVF), belong to the most common but also most underestimated zoonoses in the world. A small number of reports described the so-called 'lipid paradox' in HTVF, i.e. the striking contrast between a very low serum total cholesterol and/or high-density lipoprotein cholesterol (HDLc), and a paradoxical concomitant hypertriglyceridaemia. In a prospective study, with patients being their own control after illness, we wanted to verify if this quick and easy 'bedside test' was robust enough to warrant a preliminary diagnosis of acute kidney injury (AKI) caused by HTVF. The study cohort consisted of 58 Belgian cases (mean age 44 years), admitted with varying degrees of AKI and of thrombocytopaenia, both characteristic for presumptive HTVF. All cases were sero-confirmed as having acute HTVF. At or shortly after hospital admission, a significant (p < 0.001) decrease of total cholesterol and HDLc was found in comparison with normalised levels in the same cohort, quantified a few days after spontaneous AKI recovery. Conversely, fasting triglyceride levels during HTVF infection were significantly (p < 0.001) higher during illness than after recovery. This 'lipid paradox' was most outspoken in severe HTVF cases, often accompanying, or even predicting, major kidney or lung complications. Thus, this 'bedside assessment' seems to hold even promise for presumptive diagnosis of more severe so-called 'hantavirus cardio-pulmonary syndrome' (HCPS) cases, mostly described hitherto in the New World. In more severe AKI cases, the mean total cholesterol was significantly lower (p = 0.02) than in milder cases, i.e. cases with peak serum creatinine levels of < 1.5 mg/dL. Thrombocytopaenia, generally accepted as the severity index in HTVF, appeared, moreover, significantly correlated with serum levels of total cholesterol (R = 0.52, p < 0.001) and with serum levels of HDLc (R = 0.45, p < 0.01). A link

Early diagnosis of hantavirus infection by family doctors can reduce inappropriate antibiotic use and hospitalization.

PubMed

Brorstad, Alette; Oscarsson, Kristina Bergstedt; Ahlm, Clas

2010-09-01

Hantavirus infections are emerging infections that cause either Hantavirus pulmonary syndrome or haemorrhagic fever with renal syndrome (HFRS). A recent Swedish outbreak of nephropathia epidemica, a European HFRS, was analysed to study the patient flow and clinical picture and to investigate the value of an early diagnosis in general practice. Design. In a retrospective design, medical records of verified cases of Hantavirus infection were studied. The study was conducted in the county of Norrbotten, Sweden. Data from Hantavirus patients diagnosed between 2006 and 2008 were analysed. Demographic data, level of care, treatment, clinical symptoms, and laboratory findings were obtained. In total, 456 cases were included (58% males and 42% females). The majority of patients first saw their general practitioner and were exclusively treated in general practice (83% and 56%, respectively). When diagnosed correctly at the first visit, antibiotics and hospitalization were significantly lowered compared with delayed diagnosis (14% vs. 53% and 30% vs. 54%, respectively; p < 0.0001). The clinical picture was diverse. Early thrombocytopenia was found in 65% of the patients, and haemorrhagic manifestations were documented in a few cases. Signs of renal involvement--haematuria, proteinuria, and raised levels of serum creatinine--were found in a majority of patients. Raised awareness in general practice regarding emerging infections and better diagnostic tools are desirable. This study of a Hantavirus outbreak shows that general practitioners are frontline doctors during outbreaks and through early and correct diagnosis they can reduce antibiotic treatment and hospitalization.

Inhibition of the Hantavirus Fusion Process by Predicted Domain III and Stem Peptides from Glycoprotein Gc.

PubMed

Barriga, Gonzalo P; Villalón-Letelier, Fernando; Márquez, Chantal L; Bignon, Eduardo A; Acuña, Rodrigo; Ross, Breyan H; Monasterio, Octavio; Mardones, Gonzalo A; Vidal, Simon E; Tischler, Nicole D

2016-07-01

Hantaviruses can cause hantavirus pulmonary syndrome or hemorrhagic fever with renal syndrome in humans. To enter cells, hantaviruses fuse their envelope membrane with host cell membranes. Previously, we have shown that the Gc envelope glycoprotein is the viral fusion protein sharing characteristics with class II fusion proteins. The ectodomain of class II fusion proteins is composed of three domains connected by a stem region to a transmembrane anchor in the viral envelope. These fusion proteins can be inhibited through exogenous fusion protein fragments spanning domain III (DIII) and the stem region. Such fragments are thought to interact with the core of the fusion protein trimer during the transition from its pre-fusion to its post-fusion conformation. Based on our previous homology model structure for Gc from Andes hantavirus (ANDV), here we predicted and generated recombinant DIII and stem peptides to test whether these fragments inhibit hantavirus membrane fusion and cell entry. Recombinant ANDV DIII was soluble, presented disulfide bridges and beta-sheet secondary structure, supporting the in silico model. Using DIII and the C-terminal part of the stem region, the infection of cells by ANDV was blocked up to 60% when fusion of ANDV occurred within the endosomal route, and up to 95% when fusion occurred with the plasma membrane. Furthermore, the fragments impaired ANDV glycoprotein-mediated cell-cell fusion, and cross-inhibited the fusion mediated by the glycoproteins from Puumala virus (PUUV). The Gc fragments interfered in ANDV cell entry by preventing membrane hemifusion and pore formation, retaining Gc in a non-resistant homotrimer stage, as described for DIII and stem peptide inhibitors of class II fusion proteins. Collectively, our results demonstrate that hantavirus Gc shares not only structural, but also mechanistic similarity with class II viral fusion proteins, and will hopefully help in developing novel therapeutic strategies against hantaviruses.

Application of MODIS GPP to Forecast Risk of Hantavirus Pulmonary Syndrome Based on Fluctuations in Reservoir Population Density

NASA Astrophysics Data System (ADS)

Loehman, R.; Heinsch, F. A.; Mills, J. N.; Wagoner, K.; Running, S.

2003-12-01

Recent predictive models for hantavirus pulmonary syndrome (HPS) have used remotely sensed spectral reflectance data to characterize risk areas with limited success. We present an alternative method using gross primary production (GPP) from the MODIS sensor to estimate the effects of biomass accumulation on population density of Peromyscus maniculatus (deer mouse), the principal reservoir species for Sin Nombre virus (SNV). The majority of diagnosed HPS cases in North America are attributed to SNV, which is transmitted to humans through inhalation of excretions and secretions from infected rodents. A logistic model framework is used to evaluate MODIS GPP, temperature, and precipitation as predictors of P. maniculatus density at established trapping sites across the western United States. Rodent populations are estimated using monthly minimum number alive (MNA) data for 2000 through 2002. Both local meteorological data from nearby weather stations and 1.25 degree x 1 degree gridded data from the NASA DAO were used in the regression model to determine the spatial sensitivity of the response. MODIS eight-day GPP data (1-km resolution) were acquired and binned to monthly average and monthly sum GPP for 3km x 3km grids surrounding each rodent trapping site. The use of MODIS GPP to forecast HPS risk may result in a marked improvement over past reflectance-based risk area characterizations. The MODIS GPP product provides a vegetation dynamics estimate that is unique to disease models, and targets the fundamental ecological processes responsible for increased rodent density and amplified disease risk.

Depletion of Alveolar Macrophages Does Not Prevent Hantavirus Disease Pathogenesis in Golden Syrian Hamsters.

PubMed

Hammerbeck, Christopher D; Brocato, Rebecca L; Bell, Todd M; Schellhase, Christopher W; Mraz, Steven R; Queen, Laurie A; Hooper, Jay W

2016-07-15

Andes virus (ANDV) is associated with a lethal vascular leak syndrome in humans termed hantavirus pulmonary syndrome (HPS). The mechanism for the massive vascular leakage associated with HPS is poorly understood; however, dysregulation of components of the immune response is often suggested as a possible cause. Alveolar macrophages are found in the alveoli of the lung and represent the first line of defense to many airborne pathogens. To determine whether alveolar macrophages play a role in HPS pathogenesis, alveolar macrophages were depleted in an adult rodent model of HPS that closely resembles human HPS. Syrian hamsters were treated, intratracheally, with clodronate-encapsulated liposomes or control liposomes and were then challenged with ANDV. Treatment with clodronate-encapsulated liposomes resulted in significant reduction in alveolar macrophages, but depletion did not prevent pathogenesis or prolong disease. Depletion also did not significantly reduce the amount of virus in the lung of ANDV-infected hamsters but altered neutrophil recruitment, MIP-1α and MIP-2 chemokine expression, and vascular endothelial growth factor (VEGF) levels in hamster bronchoalveolar lavage (BAL) fluid early after intranasal challenge. These data demonstrate that alveolar macrophages may play a limited protective role early after exposure to aerosolized ANDV but do not directly contribute to hantavirus disease pathogenesis in the hamster model of HPS. Hantaviruses continue to cause disease worldwide for which there are no FDA-licensed vaccines, effective postexposure prophylactics, or therapeutics. Much of this can be attributed to a poor understanding of the mechanism of hantavirus disease pathogenesis. Hantavirus disease has long been considered an immune-mediated disease; however, by directly manipulating the Syrian hamster model, we continue to eliminate individual immune cell types. As the most numerous immune cells present in the respiratory tract, alveolar macrophages are

Depletion of Alveolar Macrophages Does Not Prevent Hantavirus Disease Pathogenesis in Golden Syrian Hamsters

PubMed Central

Hammerbeck, Christopher D.; Brocato, Rebecca L.; Bell, Todd M.; Schellhase, Christopher W.; Mraz, Steven R.; Queen, Laurie A.

2016-01-01

ABSTRACT Andes virus (ANDV) is associated with a lethal vascular leak syndrome in humans termed hantavirus pulmonary syndrome (HPS). The mechanism for the massive vascular leakage associated with HPS is poorly understood; however, dysregulation of components of the immune response is often suggested as a possible cause. Alveolar macrophages are found in the alveoli of the lung and represent the first line of defense to many airborne pathogens. To determine whether alveolar macrophages play a role in HPS pathogenesis, alveolar macrophages were depleted in an adult rodent model of HPS that closely resembles human HPS. Syrian hamsters were treated, intratracheally, with clodronate-encapsulated liposomes or control liposomes and were then challenged with ANDV. Treatment with clodronate-encapsulated liposomes resulted in significant reduction in alveolar macrophages, but depletion did not prevent pathogenesis or prolong disease. Depletion also did not significantly reduce the amount of virus in the lung of ANDV-infected hamsters but altered neutrophil recruitment, MIP-1α and MIP-2 chemokine expression, and vascular endothelial growth factor (VEGF) levels in hamster bronchoalveolar lavage (BAL) fluid early after intranasal challenge. These data demonstrate that alveolar macrophages may play a limited protective role early after exposure to aerosolized ANDV but do not directly contribute to hantavirus disease pathogenesis in the hamster model of HPS. IMPORTANCE Hantaviruses continue to cause disease worldwide for which there are no FDA-licensed vaccines, effective postexposure prophylactics, or therapeutics. Much of this can be attributed to a poor understanding of the mechanism of hantavirus disease pathogenesis. Hantavirus disease has long been considered an immune-mediated disease; however, by directly manipulating the Syrian hamster model, we continue to eliminate individual immune cell types. As the most numerous immune cells present in the respiratory tract

Hantavirus immunology of rodent reservoirs: current status and future directions.

PubMed

Schountz, Tony; Prescott, Joseph

2014-03-14

Hantaviruses are hosted by rodents, insectivores and bats. Several rodent-borne hantaviruses cause two diseases that share many features in humans, hemorrhagic fever with renal syndrome in Eurasia or hantavirus cardiopulmonary syndrome in the Americas. It is thought that the immune response plays a significant contributory role in these diseases. However, in reservoir hosts that have been closely examined, little or no pathology occurs and infection is persistent despite evidence of adaptive immune responses. Because most hantavirus reservoirs are not model organisms, it is difficult to conduct meaningful experiments that might shed light on how the viruses evade sterilizing immune responses and why immunopathology does not occur. Despite these limitations, recent advances in instrumentation and bioinformatics will have a dramatic impact on understanding reservoir host responses to hantaviruses by employing a systems biology approach to identify important pathways that mediate virus/reservoir relationships.

Hantavirus Immunology of Rodent Reservoirs: Current Status and Future Directions

PubMed Central

Schountz, Tony; Prescott, Joseph

2014-01-01

Hantaviruses are hosted by rodents, insectivores and bats. Several rodent-borne hantaviruses cause two diseases that share many features in humans, hemorrhagic fever with renal syndrome in Eurasia or hantavirus cardiopulmonary syndrome in the Americas. It is thought that the immune response plays a significant contributory role in these diseases. However, in reservoir hosts that have been closely examined, little or no pathology occurs and infection is persistent despite evidence of adaptive immune responses. Because most hantavirus reservoirs are not model organisms, it is difficult to conduct meaningful experiments that might shed light on how the viruses evade sterilizing immune responses and why immunopathology does not occur. Despite these limitations, recent advances in instrumentation and bioinformatics will have a dramatic impact on understanding reservoir host responses to hantaviruses by employing a systems biology approach to identify important pathways that mediate virus/reservoir relationships. PMID:24638205

Maripa Hantavirus in French Guiana: Phylogenetic Position and Predicted Spatial Distribution of Rodent Hosts

PubMed Central

de Thoisy, Benoît; Matheus, Séverine; Catzeflis, François; Clément, Luc; Barrioz, Sébastien; Guidez, Amandine; Donato, Damien; Cornu, Jean-François; Brunaux, Olivier; Guitet, Stéphane; Lacoste, Vincent; Lavergne, Anne

2014-01-01

A molecular screening of wild-caught rodents was conducted in French Guiana, South America to identify hosts of the hantavirus Maripa described in 2008 in a hantavirus pulmonary syndrome (HPS) case. Over a 9-year period, 418 echimyids and murids were captured. Viral RNA was detected in two sigmodontine rodents, Oligoryzomys fulvescens and Zygodontomys brevicauda, trapped close to the house of a second HPS case that occurred in 2009 and an O. fulvescens close to the fourth HPS case identified in 2013. Sequences from the rodents had 96% and 97% nucleotide identity (fragment of S and M segments, respectively) with the sequence of the first human HPS case. Phylogenetic reconstructions based on the complete sequence of the S segment show that Maripa virus is closely related to Rio Mamore hantavirus. Using environmental descriptors of trapping sites, including vegetation, landscape units, rain, and human disturbance, a maximal entropy-based species distribution model allowed for identification of areas of higher predicted occurrence of the two rodents, where emergence risks of Maripa virus are expected to be higher. PMID:24752689

What Do We Know about How Hantaviruses Interact with Their Different Hosts?

PubMed Central

Ermonval, Myriam; Baychelier, Florence; Tordo, Noël

2016-01-01

Hantaviruses, like other members of the Bunyaviridae family, are emerging viruses that are able to cause hemorrhagic fevers. Occasional transmission to humans is due to inhalation of contaminated aerosolized excreta from infected rodents. Hantaviruses are asymptomatic in their rodent or insectivore natural hosts with which they have co-evolved for millions of years. In contrast, hantaviruses cause different pathologies in humans with varying mortality rates, depending on the hantavirus species and its geographic origin. Cases of hemorrhagic fever with renal syndrome (HFRS) have been reported in Europe and Asia, while hantavirus cardiopulmonary syndromes (HCPS) are observed in the Americas. In some cases, diseases caused by Old World hantaviruses exhibit HCPS-like symptoms. Although the etiologic agents of HFRS were identified in the early 1980s, the way hantaviruses interact with their different hosts still remains elusive. What are the entry receptors? How do hantaviruses propagate in the organism and how do they cope with the immune system? This review summarizes recent data documenting interactions established by pathogenic and nonpathogenic hantaviruses with their natural or human hosts that could highlight their different outcomes. PMID:27529272

Mechanistic Insight into Bunyavirus-Induced Membrane Fusion from Structure-Function Analyses of the Hantavirus Envelope Glycoprotein Gc

PubMed Central

Stettner, Eva; Jeffers, Scott Allen; Pérez-Vargas, Jimena; Pehau-Arnaudet, Gerard; Tortorici, M. Alejandra; Jestin, Jean-Luc; England, Patrick; Tischler, Nicole D.; Rey, Félix A.

2016-01-01

Hantaviruses are zoonotic viruses transmitted to humans by persistently infected rodents, giving rise to serious outbreaks of hemorrhagic fever with renal syndrome (HFRS) or of hantavirus pulmonary syndrome (HPS), depending on the virus, which are associated with high case fatality rates. There is only limited knowledge about the organization of the viral particles and in particular, about the hantavirus membrane fusion glycoprotein Gc, the function of which is essential for virus entry. We describe here the X-ray structures of Gc from Hantaan virus, the type species hantavirus and responsible for HFRS, both in its neutral pH, monomeric pre-fusion conformation, and in its acidic pH, trimeric post-fusion form. The structures confirm the prediction that Gc is a class II fusion protein, containing the characteristic β-sheet rich domains termed I, II and III as initially identified in the fusion proteins of arboviruses such as alpha- and flaviviruses. The structures also show a number of features of Gc that are distinct from arbovirus class II proteins. In particular, hantavirus Gc inserts residues from three different loops into the target membrane to drive fusion, as confirmed functionally by structure-guided mutagenesis on the HPS-inducing Andes virus, instead of having a single “fusion loop”. We further show that the membrane interacting region of Gc becomes structured only at acidic pH via a set of polar and electrostatic interactions. Furthermore, the structure reveals that hantavirus Gc has an additional N-terminal “tail” that is crucial in stabilizing the post-fusion trimer, accompanying the swapping of domain III in the quaternary arrangement of the trimer as compared to the standard class II fusion proteins. The mechanistic understandings derived from these data are likely to provide a unique handle for devising treatments against these human pathogens. PMID:27783711

Mechanistic Insight into Bunyavirus-Induced Membrane Fusion from Structure-Function Analyses of the Hantavirus Envelope Glycoprotein Gc.

PubMed

Guardado-Calvo, Pablo; Bignon, Eduardo A; Stettner, Eva; Jeffers, Scott Allen; Pérez-Vargas, Jimena; Pehau-Arnaudet, Gerard; Tortorici, M Alejandra; Jestin, Jean-Luc; England, Patrick; Tischler, Nicole D; Rey, Félix A

2016-10-01

Hantaviruses are zoonotic viruses transmitted to humans by persistently infected rodents, giving rise to serious outbreaks of hemorrhagic fever with renal syndrome (HFRS) or of hantavirus pulmonary syndrome (HPS), depending on the virus, which are associated with high case fatality rates. There is only limited knowledge about the organization of the viral particles and in particular, about the hantavirus membrane fusion glycoprotein Gc, the function of which is essential for virus entry. We describe here the X-ray structures of Gc from Hantaan virus, the type species hantavirus and responsible for HFRS, both in its neutral pH, monomeric pre-fusion conformation, and in its acidic pH, trimeric post-fusion form. The structures confirm the prediction that Gc is a class II fusion protein, containing the characteristic β-sheet rich domains termed I, II and III as initially identified in the fusion proteins of arboviruses such as alpha- and flaviviruses. The structures also show a number of features of Gc that are distinct from arbovirus class II proteins. In particular, hantavirus Gc inserts residues from three different loops into the target membrane to drive fusion, as confirmed functionally by structure-guided mutagenesis on the HPS-inducing Andes virus, instead of having a single "fusion loop". We further show that the membrane interacting region of Gc becomes structured only at acidic pH via a set of polar and electrostatic interactions. Furthermore, the structure reveals that hantavirus Gc has an additional N-terminal "tail" that is crucial in stabilizing the post-fusion trimer, accompanying the swapping of domain III in the quaternary arrangement of the trimer as compared to the standard class II fusion proteins. The mechanistic understandings derived from these data are likely to provide a unique handle for devising treatments against these human pathogens.

[Hantavirus as important emerging agents in South America].

PubMed

Ondoño, Andrés F; Levis, Silvana; Rodas, Juan D

2011-01-01

The dawning of the 20th century was marked by the emergence of new infectious disease agents and the appearance of others previously thought controlled. Both phenomena were possibly connected with ecological disturbances that led to the recognition of a dramatic climate change, of which the effects are only now becoming noticeable. Among the variety of agents to be considered, the many new viruses stand out, not only for their numerical proliferation, but also for their genetic versatility. It is this quality that provides them dexterity for evolving new strategies and adaptations to changing environmental conditions. Recently, some of the most ubiquitous and well-publicized viral agents in the American continents have been the rodent-borne viruses, and among these are the hantaviruses, etiological agents of pulmonary syndromes. Approximately 18 hantaviruses (belonging to the family Bunyaviridae), have been discovered in South America during the last 20 years, and although most of them cause persistent infections and subclinical infections in wild rodents (particularly members of the subfamily Sigmodontinae) and humans respectively; some others might also be highly lethal for humans. The goal herein is to review the state of the art regarding general aspects of hantaviruses and the diseases they cause around the world, highlighting the most recent findings in Colombia. Finally, the many unanswered questions will be recognized and highlighted concerning clinical importance and socio-economic impact of these agents on quality of public health in Colombia.

Temporal and spatial host abundance and prevalence of Andes hantavirus in southern Argentina.

PubMed

Polop, Francisco J; Provensal, María C; Pini, Noemí; Levis, Silvana C; Priotto, José W; Enría, Delia; Calderón, Gladys E; Costa, Federico; Polop, Jaime J

2010-06-01

Andes virus (AND) is a hantavirus hosted by the sigmodontine rodent Oligoryzomys longicaudatus in southern Argentina, where it is responsible for most cases of hantavirus pulmonary syndrome (HPS). Our study provides data about the spatial variation in abundance of the rodent host of AND hantavirus. We report results of a longitudinal study performed in a locality of the Andean region of Chubut Province. From November 2003 (spring) to July 2006 (winter), O. longicaudatus was the most common species captured (63%) and it showed significant differences in abundance among habitats and seasons. Most antibody-positive rodents were O. longicaudatus (9.2%), followed by A. longipilis (3.6%) and A. olivaceus (1.5%). The highest number of antibody-positive animals was observed for males that belonged to the heaviest mass classes. Antibody-positive O. longicaudatus were more abundant in brush habitats. We found low richness of rodents and abundance of O. longicaudatus in areas affected by anthropogenic activity. The infection seems to be regionally persistent, but the risk to humans in a landscape would be localized. To develop accurate models for predicting HPS outbreaks, further research is needed to characterize rodent movement patterns across the landscape.

Hantaan Virus Nucleocapsid Protein Binds to Importin alpha Proteins and Inhibits Tumor Necrosis Factor Alpha-Induced Activation of Nuclear Factor Kappa B

DTIC Science & Technology

2008-11-19

two dis- tinct types of human disease: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) * Corresponding author ...School of Medicine, New York, New York 100292 Received 12 May 2008/Accepted 14 November 2008 Hantaviruses such as Hantaan virus (HTNV) and Andes virus...cause two human diseases, hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome, respectively. For both, disease pathogenesis is

Maripa hantavirus in French Guiana: phylogenetic position and predicted spatial distribution of rodent hosts.

PubMed

de Thoisy, Benoît; Matheus, Séverine; Catzeflis, François; Clément, Luc; Barrioz, Sébastien; Guidez, Amandine; Donato, Damien; Cornu, Jean-François; Brunaux, Olivier; Guitet, Stéphane; Lacoste, Vincent; Lavergne, Anne

2014-06-01

A molecular screening of wild-caught rodents was conducted in French Guiana, South America to identify hosts of the hantavirus Maripa described in 2008 in a hantavirus pulmonary syndrome (HPS) case. Over a 9-year period, 418 echimyids and murids were captured. Viral RNA was detected in two sigmodontine rodents, Oligoryzomys fulvescens and Zygodontomys brevicauda, trapped close to the house of a second HPS case that occurred in 2009 and an O. fulvescens close to the fourth HPS case identified in 2013. Sequences from the rodents had 96% and 97% nucleotide identity (fragment of S and M segments, respectively) with the sequence of the first human HPS case. Phylogenetic reconstructions based on the complete sequence of the S segment show that Maripa virus is closely related to Rio Mamore hantavirus. Using environmental descriptors of trapping sites, including vegetation, landscape units, rain, and human disturbance, a maximal entropy-based species distribution model allowed for identification of areas of higher predicted occurrence of the two rodents, where emergence risks of Maripa virus are expected to be higher. © The American Society of Tropical Medicine and Hygiene.

Sin Nombre virus-specific immunoglobulin M and G kinetics in hantavirus pulmonary syndrome and the role played by serologic responses in predicting disease outcome.

PubMed

MacNeil, Adam; Comer, James A; Ksiazek, Thomas G; Rollin, Pierre E

2010-07-15

Sin Nombre virus (SNV) is the primary cause of hantavirus pulmonary syndrome (HPS) in the United States. Although other studies have demonstrated a possible association between neutralizing antibody titers and the severity of HPS, the exact nature of serologic responses and their association with outcomes have not been fully characterized. We examined immunoglobulin M (IgM) and immunoglobulin G (IgG) serologic responses in 94 clinical samples from 81 patients with confirmed HPS. We further compared a subset of 31 patients with fatal HPS and 20 surviving patients for whom samples were available within a week after the onset of HPS. SNV-specific IgM antibodies displayed a trend suggesting an early peak, whereas IgG antibody values peaked later. Among individuals with samples from the first week after the onset of HPS, all surviving patients had SNV-specific IgG responses, compared with <50% of patients with fatal HPS, and the distribution of IgG responses was significantly higher in surviving patients. Production of SNV-specific IgM antibodies occurs early during the clinical course of HPS, whereas production of IgG antibodies may be more protracted. The presence and overall distribution of higher IgG antibody titers in surviving patients with HPS suggests that production of SNV-specific IgG may be a strong predictor of favorable outcomes.

Alimentary Tract as Entry Route for Hantavirus Infection

DTIC Science & Technology

Hantaviruses are zoonotic agents that cause hemorrhagic fever with renal and/or cardiopulmonary manifestations, reaching fatality rates of up to 50...predominant endemic hantavirus in Europe, is associated with mild forms of hemorrhagic fever with renal syndrome. PUUV is transmitted to humans by exposure to...viral association with endosomal antigen EEA-1, followed by virus replication and loss of epithelial barrier function with concomitant basolateral

The relative abundance of deer mice with antibody to Sin Nombre virus corresponds to the occurrence of hantavirus pulmonary syndrome in nearby humans.

PubMed

Calisher, Charles H; Mills, James N; Root, Jon Jeffrey; Doty, Jeffrey B; Beaty, Barry J

2011-05-01

Sin Nombre virus (SNV) is the principal cause of hantavirus pulmonary syndrome (HPS) in the United States and deer mice (Peromyscus maniculatus) are its principal rodent host, and thus the natural cycle of the virus is related to the occurrence of HPS. Prevalence of rodent infection appears to be associated with fluctuations in deer mouse populations and, indirectly, with timing and amount of precipitation, a complex of biologic events. Given that rodent population abundances fluctuate, often acutely, it is not unreasonable to assume a direct correlation between the numbers of infected rodents and the number of human infections, unless confounding factors are involved. During a 13-year longitudinal study at a site in southwestern Colorado, we accumulated data regarding deer mice and antibody to SNV and therefore had the opportunity to compare dynamics of deer mouse populations, seroprevalence of antibody to SNV in the rodents, and numbers of HPS cases in Durango and in the State of Colorado as a whole. If abundances of deer mouse populations are directly correlated with occurrence of HPS, it is reasonable to assume that low densities of deer mice and low prevalences of antibody to SNV would lead to fewer human cases than would high densities and high prevalences. Our results substantiate such an assumption and suggest that the risk of acquisition of HPS is likely related to both high numbers of infected deer mice and human activities, rather than being strictly related to prevalence of SNV in the host rodent.

The adaptive immune response does not influence hantavirus disease or persistence in the Syrian hamster

PubMed Central

Prescott, Joseph; Safronetz, David; Haddock, Elaine; Robertson, Shelly; Scott, Dana; Feldmann, Heinz

2013-01-01

Pathogenic New World hantaviruses cause severe disease in humans characterized by a vascular leak syndrome, leading to pulmonary oedema and respiratory distress with case fatality rates approaching 40%. Hantaviruses infect microvascular endothelial cells without conspicuous cytopathic effects, indicating that destruction of the endothelium is not a mechanism of disease. In humans, high levels of inflammatory cytokines are present in the lungs of patients that succumb to infection. This, along with other observations, suggests that disease has an immunopathogenic component. Currently the only animal model available to study hantavirus disease is the Syrian hamster, where infection with Andes virus (ANDV), the primary agent of disease in South America, results in disease that closely mimics that seen in humans. Conversely, inoculation of hamsters with a passaged Sin Nombre virus (SNV), the virus responsible for most cases of disease in North America, results in persistent infection with high levels of viral replication. We found that ANDV elicited a stronger innate immune response, whereas SNV elicited a more robust adaptive response in the lung. Additionally, ANDV infection resulted in significant changes in the blood lymphocyte populations. To determine whether the adaptive immune response influences infection outcome, we depleted hamsters of CD4+ and CD8+ T cells before infection with hantaviruses. Depletion resulted in inhibition of virus-specific antibody responses, although the pathogenesis and replication of these viruses were unaltered. These data show that neither hantavirus replication, nor pathogenesis caused by these viruses, is influenced by the adaptive immune response in the Syrian hamster. PMID:23600567

Confirmation of Choclo virus as the cause of hantavirus cardiopulmonary syndrome and high serum antibody prevalence in Panama.

PubMed

Nelson, Randin; Cañate, Raul; Pascale, Juan Miguel; Dragoo, Jerry W; Armien, Blas; Armien, Anibal G; Koster, Frederick

2010-09-01

Choclo virus (CHOV) was described in sigmodontine rodents, Oligoryzomys fulvescens, and humans during an outbreak of hantavirus cardiopulmonary syndrome (HCPS) in 1999-2000 in western Panama. Although HCPS is rare, hantavirus-specific serum antibody prevalence among the general population is high suggesting that CHOV may cause many mild or asymptomatic infections. The goals of this study were to confirm the role of CHOV in HCPS and in the frequently detected serum antibody and to establish the phylogenetic relationship with other New World hantaviruses. CHOV was cultured to facilitate the sequencing of the small (S) and medium (M) segments and to perform CHOV-specific serum neutralization antibody assays. Sequences of the S and M segments found a close relationship to other Oligoryzomys-borne hantaviruses in the Americas, highly conserved terminal nucleotides, and no evidence for recombination events. The maximum likelihood and maximum parsimony analyses of complete M segment nucleotide sequences indicate a close relationship to Maporal and Laguna Negra viruses, found at the base of the South American clade. In a focus neutralization assay acute and convalescent sera from six Panamanian HCPS patients neutralized CHOV in dilutions from 1:200 to 1:6,400. In a sample of antibody-positive adults without a history of HCPS, 9 of 10 sera neutralized CHOV in dilutions ranging from 1:100 to 1:6,400. Although cross-neutralization with other sympatric hantaviruses not yet associated with human disease is possible, CHOV appears to be the causal agent for most of the mild or asymptomatic hantavirus infections, as well as HCPS, in Panama.

Distributional ecology of Andes hantavirus: a macroecological approach.

PubMed

Astorga, Francisca; Escobar, Luis E; Poo-Muñoz, Daniela; Escobar-Dodero, Joaquin; Rojas-Hucks, Sylvia; Alvarado-Rybak, Mario; Duclos, Melanie; Romero-Alvarez, Daniel; Molina-Burgos, Blanca E; Peñafiel-Ricaurte, Alexandra; Toro, Frederick; Peña-Gómez, Francisco T; Peterson, A Townsend

2018-06-22

Hantavirus pulmonary syndrome (HPS) is an infection endemic in Chile and Argentina, caused by Andes hantavirus (ANDV). The rodent Oligoryzomys longicaudatus is suggested as the main reservoir, although several other species of Sigmodontinae are known hosts of ANDV. Here, we explore potential ANDV transmission risk to humans in southern South America, based on eco-epidemiological associations among: six rodent host species, seropositive rodents, and human HPS cases. We used ecological niche modeling and macroecological approaches to determine potential geographic distributions and assess environmental similarity among rodents and human HPS cases. Highest numbers of rodent species (five) were in Chile between 35° and 41°S latitude. Background similarity tests showed niche similarity in 14 of the 56 possible comparisons: similarity between human HPS cases and the background of all species and seropositive rodents was supported (except for Abrothrix sanborni). Of interest among the results is the likely role of O. longicaudatus, Loxodontomys micropus, Abrothrix olivaceus, and Abrothrix longipilis in HPS transmission to humans. Our results support a role of rodent species' distributions as a risk factor for human HPS at coarse scales, and suggest that the role of the main reservoir (O. longicaudatus) may be supported by the broader rodent host community in some areas.

Landscape, Environmental and Social Predictors of Hantavirus Risk in São Paulo, Brazil

PubMed Central

Uriarte, Maria; Tambosi, Leandro Reverberi; Prado, Amanda; Pardini, Renata; D´Andrea, Paulo Sérgio; Metzger, Jean Paul

2016-01-01

Hantavirus Pulmonary Syndrome (HPS) is a disease caused by Hantavirus, which are negative-sense RNA viruses in the family Bunyaviridae that are highly virulent to humans. Numerous factors modify risk of Hantavirus transmission and consequent HPS risk. Human-driven landscape change can foster transmission risk by increasing numbers of habitat generalist rodent species that serve as the principal reservoir host. Climate can also affect rodent population dynamics and Hantavirus survival, and a number of social factors can influence probability of HPS transmission to humans. Evaluating contributions of these factors to HPS risk may enable predictions of future outbreaks, and is critical to development of effective public health strategies. Here we rely on a Bayesian model to quantify associations between annual HPS incidence across the state of São Paulo, Brazil (1993–2012) and climate variables (annual precipitation, annual mean temperature), landscape structure metrics (proportion of native habitat cover, number of forest fragments, proportion of area planted with sugarcane), and social factors (number of men older than 14 years and Human Development Index). We built separate models for the main two biomes of the state (cerrado and Atlantic forest). In both biomes Hantavirus risk increased with proportion of land cultivated for sugarcane and HDI, but proportion of forest cover, annual mean temperature, and population at risk also showed positive relationships in the Atlantic forest. Our analysis provides the first evidence that social, landscape, and climate factors are associated with HPS incidence in the Neotropics. Our risk map can be used to support the adoption of preventive measures and optimize the allocation of resources to avoid disease propagation, especially in municipalities that show medium to high HPS risk (> 5% of risk), and aimed at sugarcane workers, minimizing the risk of future HPS outbreaks. PMID:27780250

Serological Evidence of Hantavirus Infection in Apparently Healthy People from Rural and Slum Communities in Southern Chile

PubMed Central

Muñoz-Zanzi, Claudia; Saavedra, Farides; Otth, Carola; Domancich, Ljubica; Hott, Melissa; Padula, Paula

2015-01-01

Hantavirus disease in America has been recognizable because of its rapid progression in clinical cases, occurrence in previously healthy young adults, and high case fatality rate. Hantavirus disease has been proposed now to define the diversity of clinical manifestations. Since 1995, a total of 902 cases of hantavirus pulmonary syndrome have been reported in Chile, caused by Andes virus (ANDV), with overall fatality of 32%. This report describes the sero-epidemiology of hantavirus in apparently healthy people in rural and urban slum communities from southern Chile. Ten of 934 samples yielded a positive result resulting in a seroprevalence of 1.07% (95% confidence intervals: 0.05%–2.0%). A higher proportion of positive samples was found among individuals from rural villages (1.3%) and slums (1.5%) compared with farms (0.5%). Seropositivity was associated with age (p = 0.011), low education level (p = 0.006) and occupations linked to the household (homemaker, retired, or student) (p = 0.016). No evidence of infection was found in 38 sigmodontinae rodents trapped in the peri-domestic environment. Our findings highlight that exposure risk was associated with less documented risk factors, such as women in slum and rural villages, and the occurrence of infection that may have presented as flu-like illness that did not require medical attention or was misdiagnosed. PMID:25912713

The adaptive immune response does not influence hantavirus disease or persistence in the Syrian hamster.

PubMed

Prescott, Joseph; Safronetz, David; Haddock, Elaine; Robertson, Shelly; Scott, Dana; Feldmann, Heinz

2013-10-01

Pathogenic New World hantaviruses cause severe disease in humans characterized by a vascular leak syndrome, leading to pulmonary oedema and respiratory distress with case fatality rates approaching 40%. Hantaviruses infect microvascular endothelial cells without conspicuous cytopathic effects, indicating that destruction of the endothelium is not a mechanism of disease. In humans, high levels of inflammatory cytokines are present in the lungs of patients that succumb to infection. This, along with other observations, suggests that disease has an immunopathogenic component. Currently the only animal model available to study hantavirus disease is the Syrian hamster, where infection with Andes virus (ANDV), the primary agent of disease in South America, results in disease that closely mimics that seen in humans. Conversely, inoculation of hamsters with a passaged Sin Nombre virus (SNV), the virus responsible for most cases of disease in North America, results in persistent infection with high levels of viral replication. We found that ANDV elicited a stronger innate immune response, whereas SNV elicited a more robust adaptive response in the lung. Additionally, ANDV infection resulted in significant changes in the blood lymphocyte populations. To determine whether the adaptive immune response influences infection outcome, we depleted hamsters of CD4(+) and CD8(+) T cells before infection with hantaviruses. Depletion resulted in inhibition of virus-specific antibody responses, although the pathogenesis and replication of these viruses were unaltered. These data show that neither hantavirus replication, nor pathogenesis caused by these viruses, is influenced by the adaptive immune response in the Syrian hamster. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Hantaviruses in Africa.

PubMed

Witkowski, Peter T; Klempa, Boris; Ithete, Ndapewa L; Auste, Brita; Mfune, John K E; Hoveka, Julia; Matthee, Sonja; Preiser, Wolfgang; Kruger, Detlev H

2014-07-17

This paper summarizes the progress in the search for hantaviruses and hantavirus infections in Africa. After having collected molecular evidence of an indigenous African hantavirus in 2006, an intensive investigation for new hantaviruses has been started in small mammals. Various novel hantaviruses have been molecularly identified not only in rodents but also in shrews and bats. In addition, the first African hantavirus, Sangassou virus, has been isolated and functionally characterized in cell culture. Less is known about the ability of these hantaviruses to infect humans and to cause diseases. To date, no hantavirus genetic material could be amplified from patients' specimens collected in Africa. Serological studies in West Africa, based on a battery of screening and confirmatory assays, led to the detection of hantavirus antibodies in the human population and in patients with putative hantavirus disease. In addition to this overview, we present original data from seroepidemiological and field studies conducted in the Southern part of Africa. A human seroprevalence rate of 1.0% (n=1442) was detected in the South African Cape Region whereas no molecular evidence for the presence of hantavirus was found in 2500 small animals trapped in South Africa and Namibia. Copyright © 2014 Elsevier B.V. All rights reserved.

Hantavirus Pulmonary Syndrome in Central Bolivia: Relationships Between Reservoir Hosts, Habitats, and Viral Genotypes

DTIC Science & Technology

2005-01-01

in Brazil. J Med Virol 59: 527–535. 7. Lopez N, Padula P, Rossi C, Lazaro ME, Franze-Fernandez MT, 1996. Genetic identification of a new hantavirus...177: 529–538. 10. Toro J, Vega JD, Khan AS, Mills JN, Padula P, Terry W, Yadon Z, Valderrama R, Ellis BA, Pavletic C, Cerda R, Zaki S, Wun- Ju S, Meyer...Chile, 1997. Emerg Infect Dis 4: 687–694. 11. Padula PJ, Rossi CM, Della Valle MO, Martinez PV, Colavecchia SB, Edelstein A, Miguel SD, Rabinovich RD

Toward a Mechanistic Understanding of Environmentally Forced Zoonotic Disease Emergence: Sin Nombre Hantavirus

PubMed Central

Carver, Scott; Mills, James N.; Parmenter, Cheryl A.; Parmenter, Robert R.; Richardson, Kyle S.; Harris, Rachel L.; Douglass, Richard J.; Kuenzi, Amy J.; Luis, Angela D.

2015-01-01

Understanding the environmental drivers of zoonotic reservoir and human interactions is crucial to understanding disease risk, but these drivers are poorly predicted. We propose a mechanistic understanding of human–reservoir interactions, using hantavirus pulmonary syndrome as a case study. Crucial processes underpinning the disease's incidence remain poorly studied, including the connectivity among natural and peridomestic deer mouse host activity, virus transmission, and human exposure. We found that disease cases were greatest in arid states and declined exponentially with increasing precipitation. Within arid environments, relatively rare climatic conditions (e.g., El Niño) are associated with increased rainfall and reservoir abundance, producing more frequent virus transmission and host dispersal. We suggest that deer mice increase their occupancy of peridomestic structures during spring–summer, amplifying intraspecific transmission and human infection risk. Disease incidence in arid states may increase with predicted climatic changes. Mechanistic approaches incorporating reservoir behavior, reservoir–human interactions, and pathogen spillover could enhance our understanding of global hantavirus ecology, with applications to other directly transmitted zoonoses. PMID:26955081

Hantavirus Public Health outreach effectiveness in three populations: an overview of northwestern New Mexico, Los Santos Panama, and Region IX Chile.

PubMed

McConnell, Marjorie S

2014-02-27

This research compared the effectiveness of Hantavirus Pulmonary Syndrome (HPS) outreach programs in New Mexico, Panama, and Chile. Understanding the role of human demographics, disease ecology, and human behavior in the disease process is critical to the examination of community responses in terms of behavior changes. Attitudes, knowledge, and behavior across three populations were measured through the implementation of a self-administered questionnaire (N = 601). Surveys implemented in Chile and Panama in 2004, followed by northwestern New Mexico in 2008, attempted to assess knowledge and behavior change with respect to hantavirus in high- and lower-risk prevalence areas during endemic periods. While levels of concern over contracting hantavirus were lowest in New Mexico, they were highest in Panama. Respondents in Chile showed mid-level concern and exhibited a tendency to practice proper cleaning methods more than in New Mexico and Panama. This indicates that public health messages appear to be more effective in Chile. However, since negative behavior changes, such as sweeping and vacuuming, occur at some level in all three populations, improved messages should help decrease risk of exposure to HPS.

Evaluation of habitat requirements of small rodents and effectiveness of an ecologically-based management in a hantavirus-endemic natural protected area in Argentina.

PubMed

Vadell, María Victoria; García Erize, Francisco; Gómez Villafañe, Isabel Elisa

2017-01-01

Hantavirus pulmonary syndrome is a severe cardio pulmonary disease transmitted to humans by sylvan rodents found in natural and rural environments. Disease transmission is closely linked to the ecology of animal reservoirs and abiotic factors such as habitat characteristics, season or climatic conditions. The main goals of this research were: to determine the biotic and abiotic factors affecting richness and abundance of rodent species at different spatial scales, to evaluate different methodologies for studying population of small rodents, and to describe and analyze an ecologically-based rodent management experience in a highly touristic area. A 4-year study of small rodent ecology was conducted between April 2007 and August 2011 in the most relevant habitats of El Palmar National Park, Argentina. Management involved a wide range of control and prevention measures, including poisoning, culling and habitat modification. A total of 172 individuals of 5 species were captured with a trapping effort of 13 860 traps-nights (1.24 individuals/100 traps-nights). Five rodent species were captured, including 2 hantavirus-host species, Oligoryzomys nigripes and Akodon azarae. Oligoryzomys nigripes, host of a hantavirus that is pathogenic in humans, was the most abundant species and the only one found in all the studied habitats. Our results are inconsistent with the dilution effect hypothesis. The present study demonstrates that sylvan rodent species, including the hantavirus-host species, have distinct local habitat selection and temporal variation patterns in abundance, which may influence the risk of human exposure to hantavirus and may have practical implications for disease transmission as well as for reservoir management. © 2016 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

Haploid Genetic Screen Reveals a Profound and Direct Dependence on Cholesterol for Hantavirus Membrane Fusion

PubMed Central

Kleinfelter, Lara M.; Jangra, Rohit K.; Jae, Lucas T.; Herbert, Andrew S.; Mittler, Eva; Stiles, Katie M.; Wirchnianski, Ariel S.; Kielian, Margaret; Brummelkamp, Thijn R.

2015-01-01

ABSTRACT Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and a highly fatal hantavirus cardiopulmonary syndrome (HCPS) in the New World. No vaccines or antiviral therapies are currently available to prevent or treat hantavirus disease, and gaps in our understanding of how hantaviruses enter cells challenge the search for therapeutics. We performed a haploid genetic screen in human cells to identify host factors required for entry by Andes virus, a highly virulent New World hantavirus. We found that multiple genes involved in cholesterol sensing, regulation, and biosynthesis, including key components of the sterol response element-binding protein (SREBP) pathway, are critical for Andes virus entry. Genetic or pharmacological disruption of the membrane-bound transcription factor peptidase/site-1 protease (MBTPS1/S1P), an SREBP control element, dramatically reduced infection by virulent hantaviruses of both the Old World and New World clades but not by rhabdoviruses or alphaviruses, indicating that this pathway is broadly, but selectively, required by hantaviruses. These results could be fully explained as arising from the modest depletion of cellular membrane cholesterol that accompanied S1P disruption. Mechanistic studies of cells and with protein-free liposomes suggested that high levels of cholesterol are specifically needed for hantavirus membrane fusion. Taken together, our results indicate that the profound dependence on target membrane cholesterol is a fundamental, and unusual, biophysical property of hantavirus glycoprotein-membrane interactions during entry. PMID:26126854

Imaging of hemorrhagic fever with renal syndrome: a potential bioterrorism agent of military significance.

PubMed

Bui-Mansfield, Liem T; Cressler, Dana K

2011-11-01

Hemorrhagic fever with renal syndrome (HFRS) is a potentially fatal infectious disease with worldwide distribution. Its etiologic agents are viruses of the genus Hantavirus of the virus family Bunyaviridae. Hypothetical ease of production and distribution of these agents, with their propensity to incapacitate victims and overwhelm health care resources, lend themselves as significant potential biological agents of terrorism. HFRS has protean clinical manifestations, which may mimic upper respiratory tract infection, nephrolithiasis, and Hantavirus pulmonary syndrome and may delay proper treatment. Sequelae of HFRS, such as hemorrhage, acute renal failure, retroperitoneal edema, pancreatitis, pulmonary edema, and neurologic symptoms, can be detected by different imaging modalities. Medical providers caring for HFRS patients must be aware of its radiologic features, which may help to confirm its clinical diagnosis. In this article, the authors review the epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, and complications of HFRS.

Differential Lymphocyte and Antibody Responses in Deer Mice Infected with Sin Nombre Hantavirus or Andes Hantavirus

PubMed Central

Quackenbush, Sandra; Rovnak, Joel; Haddock, Elaine; Black, William C.; Feldmann, Heinz; Prescott, Joseph

2014-01-01

ABSTRACT Hantavirus cardiopulmonary syndrome (HCPS) is a rodent-borne disease with a high case-fatality rate that is caused by several New World hantaviruses. Each pathogenic hantavirus is naturally hosted by a principal rodent species without conspicuous disease and infection is persistent, perhaps for life. Deer mice (Peromyscus maniculatus) are the natural reservoirs of Sin Nombre virus (SNV), the etiologic agent of most HCPS cases in North America. Deer mice remain infected despite a helper T cell response that leads to high-titer neutralizing antibodies. Deer mice are also susceptible to Andes hantavirus (ANDV), which causes most HCPS cases in South America; however, deer mice clear ANDV. We infected deer mice with SNV or ANDV to identify differences in host responses that might account for this differential outcome. SNV RNA levels were higher in the lungs but not different in the heart, spleen, or kidneys. Most ANDV-infected deer mice had seroconverted 14 days after inoculation, but none of the SNV-infected deer mice had. Examination of lymph node cell antigen recall responses identified elevated immune gene expression in deer mice infected with ANDV and suggested maturation toward a Th2 or T follicular helper phenotype in some ANDV-infected deer mice, including activation of the interleukin 4 (IL-4) pathway in T cells and B cells. These data suggest that the rate of maturation of the immune response is substantially higher and of greater magnitude during ANDV infection, and these differences may account for clearance of ANDV and persistence of SNV. IMPORTANCE Hantaviruses persistently infect their reservoir rodent hosts without pathology. It is unknown how these viruses evade sterilizing immune responses in the reservoirs. We have determined that infection of the deer mouse with its homologous hantavirus, Sin Nombre virus, results in low levels of immune gene expression in antigen-stimulated lymph node cells and a poor antibody response. However, infection

Differential lymphocyte and antibody responses in deer mice infected with Sin Nombre hantavirus or Andes hantavirus.

PubMed

Schountz, Tony; Quackenbush, Sandra; Rovnak, Joel; Haddock, Elaine; Black, William C; Feldmann, Heinz; Prescott, Joseph

2014-08-01

Hantavirus cardiopulmonary syndrome (HCPS) is a rodent-borne disease with a high case-fatality rate that is caused by several New World hantaviruses. Each pathogenic hantavirus is naturally hosted by a principal rodent species without conspicuous disease and infection is persistent, perhaps for life. Deer mice (Peromyscus maniculatus) are the natural reservoirs of Sin Nombre virus (SNV), the etiologic agent of most HCPS cases in North America. Deer mice remain infected despite a helper T cell response that leads to high-titer neutralizing antibodies. Deer mice are also susceptible to Andes hantavirus (ANDV), which causes most HCPS cases in South America; however, deer mice clear ANDV. We infected deer mice with SNV or ANDV to identify differences in host responses that might account for this differential outcome. SNV RNA levels were higher in the lungs but not different in the heart, spleen, or kidneys. Most ANDV-infected deer mice had seroconverted 14 days after inoculation, but none of the SNV-infected deer mice had. Examination of lymph node cell antigen recall responses identified elevated immune gene expression in deer mice infected with ANDV and suggested maturation toward a Th2 or T follicular helper phenotype in some ANDV-infected deer mice, including activation of the interleukin 4 (IL-4) pathway in T cells and B cells. These data suggest that the rate of maturation of the immune response is substantially higher and of greater magnitude during ANDV infection, and these differences may account for clearance of ANDV and persistence of SNV. Hantaviruses persistently infect their reservoir rodent hosts without pathology. It is unknown how these viruses evade sterilizing immune responses in the reservoirs. We have determined that infection of the deer mouse with its homologous hantavirus, Sin Nombre virus, results in low levels of immune gene expression in antigen-stimulated lymph node cells and a poor antibody response. However, infection of deer mice with a

Cytotoxic immune responses in the lungs correlate to disease severity in patients with hantavirus infection.

PubMed

Rasmuson, J; Pourazar, J; Mohamed, N; Lejon, K; Evander, M; Blomberg, A; Ahlm, C

2016-04-01

Hantavirus infections may cause severe and sometime life-threatening lung failure. The pathogenesis is not fully known and there is an urgent need for effective treatment. We aimed to investigate the association between pulmonary viral load and immune responses, and their relation to disease severity. Bronchoscopy with sampling of bronchoalveolar lavage (BAL) fluid was performed in 17 patients with acute Puumala hantavirus infection and 16 healthy volunteers acting as controls. Lymphocyte subsets, granzyme concentrations, and viral load were determined by flow cytometry, enzyme-linked immunosorbent assay (ELISA), and quantitative reverse transcription polymerase chain reaction (RT-PCR), respectively. Analyses of BAL fluid revealed significantly higher numbers of activated CD8(+) T cells and natural killer (NK) cells, as well as higher concentrations of the cytotoxins granzymes A and B in hantavirus-infected patients, compared to controls. In patients, Puumala hantavirus RNA was detected in 88 % of BAL cell samples and correlated inversely to the T cell response. The magnitude of the pulmonary cytotoxic lymphocyte response correlated to the severity of disease and systemic organ dysfunction, in terms of need for supplemental oxygen treatment, hypotension, and laboratory data indicating renal failure, cardiac dysfunction, vascular leakage, and cell damage. Regulatory T cell numbers were significantly lower in patients compared to controls, and may reflect inadequate immune regulation during hantavirus infection. Hantavirus infection elicits a pronounced cytotoxic lymphocyte response in the lungs. The magnitude of the immune response was associated with disease severity. These results give insights into the pathogenesis and possibilities for new treatments.

Immune Serum Produced by DNA Vaccination Protects Hamsters against Lethal Respiratory Challenge with Andes Virus

DTIC Science & Technology

2008-02-01

responses in the hantavirus cardiopulmonary syndrome. J. Infect. Dis. 182:43–48. 3. Butler, J. C., and C. J. Peters. 1994. Hantaviruses and hantavirus ...November 2007 Hantavirus pulmonary syndrome (HPS) is a highly pathogenic disease (40% case fatality rate) carried by rodents chronically infected with...certain viruses within the genus Hantavirus of the family Bunyaviridae. The primary mode of transmission to humans is thought to be inhalation of excreta

Development and validation of a point-of-care test for detecting hantavirus antibodies in human and rodent samples.

PubMed

Koishi, Andrea Cristine; Aoki, Mateus Nóbrega; Jorge, Taissa Ricciardi; Suzukawa, Andréia Akemi; Zanluca, Camila; Levis, Silvana; Duarte Dos Santos, Claudia Nunes

2016-07-01

Hantaviruses are etiologic agents of a zoonotic disease transmitted mainly from wild rodents to humans, causing Hemorrhagic Fever with Renal Syndrome in Eurasia and the Hantavirus Cardiopulmonary Syndrome in the Americas (HCPS), reaching a lethality rate of 40% in Brazil. Hantavirus diagnostic and seroprevalence are often based on the presence of IgM and IgG antibodies against the virus. Here we propose a rapid test assay able to identify hantavirus antibodies with sensibility and specificity similar to ELISA assays. We analyzed five groups of samples, including healthy human population and small mammals of endemic areas, suspected cases of HCPS, patients with non-related infections and a serum panel from a different geographical region. The test presented good rates of sensibility (87-100%) and specificity (97-100%) for all groups, being a promising tool suitable for both rodent and human hantavirus epidemiological surveys. Copyright © 2016 Elsevier Inc. All rights reserved.

Hantavirus Public Health Outreach Effectiveness in Three Populations: An Overview of Northwestern New Mexico, Los Santos Panama, and Region IX Chile

PubMed Central

McConnell, Marjorie S.

2014-01-01

This research compared the effectiveness of Hantavirus Pulmonary Syndrome (HPS) outreach programs in New Mexico, Panama, and Chile. Understanding the role of human demographics, disease ecology, and human behavior in the disease process is critical to the examination of community responses in terms of behavior changes. Attitudes, knowledge, and behavior across three populations were measured through the implementation of a self-administered questionnaire (N = 601). Surveys implemented in Chile and Panama in 2004, followed by northwestern New Mexico in 2008, attempted to assess knowledge and behavior change with respect to hantavirus in high- and lower-risk prevalence areas during endemic periods. While levels of concern over contracting hantavirus were lowest in New Mexico, they were highest in Panama. Respondents in Chile showed mid-level concern and exhibited a tendency to practice proper cleaning methods more than in New Mexico and Panama. This indicates that public health messages appear to be more effective in Chile. However, since negative behavior changes, such as sweeping and vacuuming, occur at some level in all three populations, improved messages should help decrease risk of exposure to HPS. PMID:24584027

Novel Insights on Hantavirus Evolution: The Dichotomy in Evolutionary Pressures Acting on Different Hantavirus Segments.

PubMed

Sankar, Sathish; Upadhyay, Mohita; Ramamurthy, Mageshbabu; Vadivel, Kumaran; Sagadevan, Kalaiselvan; Nandagopal, Balaji; Vivekanandan, Perumal; Sridharan, Gopalan

2015-01-01

Hantaviruses are important emerging zoonotic pathogens. The current understanding of hantavirus evolution is complicated by the lack of consensus on co-divergence of hantaviruses with their animal hosts. In addition, hantaviruses have long-term associations with their reservoir hosts. Analyzing the relative abundance of dinucleotides may shed new light on hantavirus evolution. We studied the relative abundance of dinucleotides and the evolutionary pressures shaping different hantavirus segments. A total of 118 sequences were analyzed; this includes 51 sequences of the S segment, 43 sequences of the M segment and 23 sequences of the L segment. The relative abundance of dinucleotides, effective codon number (ENC), codon usage biases were analyzed. Standard methods were used to investigate the relative roles of mutational pressure and translational selection on the three hantavirus segments. All three segments of hantaviruses are CpG depleted. Mutational pressure is the predominant evolutionary force leading to CpG depletion among hantaviruses. Interestingly, the S segment of hantaviruses is GpU depleted and in contrast to CpG depletion, the depletion of GpU dinucleotides from the S segment is driven by translational selection. Our findings also suggest that mutational pressure is the primary evolutionary pressure acting on the S and the M segments of hantaviruses. While translational selection plays a key role in shaping the evolution of the L segment. Our findings highlight how different evolutionary pressures may contribute disproportionally to the evolution of the three hantavirus segments. These findings provide new insights on the current understanding of hantavirus evolution. There is a dichotomy among evolutionary pressures shaping a) the relative abundance of different dinucleotides in hantavirus genomes b) the evolution of the three hantavirus segments.

Surveillance of Hantaviruses in Poland: A Study of Animal Reservoirs and Human Hantavirus Disease in Subcarpathia

PubMed Central

Niemcewicz, Marcin; Bielawska-Drózd, Agata; Nowakowska, Anna; Gaweł, Jerzy; Pitucha, Grzegorz; Joniec, Justyna; Zielonka, Katarzyna; Marciniak-Niemcewicz, Anna; Kocik, Janusz

2014-01-01

Abstract The first cluster of hemorrhagic fever with renal syndrome (HFRS) in Poland was identified in 2007 in the Subcarpathian region. The natural environment of this area is a key habitat for hantavirus vectors. The animal reservoir of existing human HFRS clusters was studied to assess the occurrence of viruses (including Tula virus, Puumala virus, and Dobrava–Belgrade virus) among rodents. We examined 70 suspected human cases with symptoms corresponding to the clinical picture of HFRS. Serological analysis (indirect immunofluorescence assay and immunoblot) confirmed the presence of anti-hantavirus antibodies in 18 patients, which were surveyed with regard to developed symptoms and presumed rodent contact. Seroepidemiological analysis of newly confirmed human cases was performed, putative areas of human exposure were studied, and 194 rodents were subsequently captured from identified areas. Internal organs (lungs, heart, spleen, bladder, and kidneys) were collected from 64 Apodemus flavicollis, 55 Apodemus agrarius, 40 Myodes glareolus, 21 Mus musculus, and 14 Microtus arvalis and tested for the presence of hantavirus RNA by reverse transcription and subsequent real-time PCR. Positive samples were also tested by indirect immunofluorescence. Animal reservoir surveillance enabled the first detection of Puumala virus and Dobrava–Belgrade virus among animals in Poland. Furthermore, some places where rodents were captured correlated with areas of residence of laboratory-confirmed human cases and likely detected virus species. Moreover, three species of hantaviruses coexisting in a relatively small area were identified. PMID:24902039

Landscape, Climate and Hantavirus Cardiopulmonary Syndrome Outbreaks.

PubMed

Prist, Paula Ribeiro; D Andrea, Paulo Sérgio; Metzger, Jean Paul

2017-09-01

We performed a literature review in order to improve our understanding of how landscape and climate drivers affect HCPS outbreaks. Anthropogenic landscape changes such as forest loss, fragmentation and agricultural land uses are related with a boost in hantavirus reservoir species abundance and hantavirus prevalence in tropical areas, increasing HCPS risk. Additionally, higher precipitation, especially in arid regions, favors an increase in vegetational biomass, which augments the resources for reservoir rodents, also increasing HCPS risk. Although these relationships were observed, few studies described it so far, and the ones that did it are concentrated in few places. To guide future research on this issue, we build a conceptual model relating landscape and climate variables with HCPS outbreaks and identified research opportunities. We point out the need for studies addressing the effects of landscape configuration, temperature and the interaction between climate and landscape variables. Critical landscape thresholds are also highly relevant, once HCPS risk transmission can increase rapidly above a certain degree of landscape degradation. These studies could be relevant to implement preventive measures, creating landscapes that can mitigate disease spread risk.

Combined Pulmonary Fibrosis and Emphysema Syndrome

PubMed Central

Rounds, Sharon I. S.

2012-01-01

There is increasing clinical, radiologic, and pathologic recognition of the coexistence of emphysema and pulmonary fibrosis in the same patient, resulting in a clinical syndrome known as combined pulmonary fibrosis and emphysema (CPFE) that is characterized by dyspnea, upper-lobe emphysema, lower-lobe fibrosis, and abnormalities of gas exchange. This syndrome frequently is complicated by pulmonary hypertension, acute lung injury, and lung cancer. The CPFE syndrome typically occurs in male smokers, and the mortality associated with this condition, especially if pulmonary hypertension is present, is significant. In this review, we explore the current state of the literature and discuss etiologic factors and clinical characteristics of the CPFE syndrome. PMID:22215830

Crystal Structure of the Core Region of Hantavirus Nucleocapsid Protein Reveals the Mechanism for Ribonucleoprotein Complex Formation

PubMed Central

Guo, Yu; Wang, Wenming; Sun, Yuna; Ma, Chao; Wang, Xu; Wang, Xin; Liu, Pi; Shen, Shu; Li, Baobin; Lin, Jianping; Deng, Fei

2015-01-01

ABSTRACT Hantaviruses, which belong to the genus Hantavirus in the family Bunyaviridae, infect mammals, including humans, causing either hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS) in humans with high mortality. Hantavirus encodes a nucleocapsid protein (NP) to encapsidate the genome and form a ribonucleoprotein complex (RNP) together with viral polymerase. Here, we report the crystal structure of the core domains of NP (NPcore) encoded by Sin Nombre virus (SNV) and Andes virus (ANDV), which are two representative members that cause HCPS in the New World. The constructs of SNV and ANDV NPcore exclude the N- and C-terminal portions of full polypeptide to obtain stable proteins for crystallographic study. The structure features an N lobe and a C lobe to clamp RNA-binding crevice and exhibits two protruding extensions in both lobes. The positively charged residues located in the RNA-binding crevice play a key role in RNA binding and virus replication. We further demonstrated that the C-terminal helix and the linker region connecting the N-terminal coiled-coil domain and NPcore are essential for hantavirus NP oligomerization through contacts made with two adjacent protomers. Moreover, electron microscopy (EM) visualization of native RNPs extracted from the virions revealed that a monomer-sized NP-RNA complex is the building block of viral RNP. This work provides insight into the formation of hantavirus RNP and provides an understanding of the evolutionary connections that exist among bunyaviruses. IMPORTANCE Hantaviruses are distributed across a wide and increasing range of host reservoirs throughout the world. In particular, hantaviruses can be transmitted via aerosols of rodent excreta to humans or from human to human and cause HFRS and HCPS, with mortalities of 15% and 50%, respectively. Hantavirus is therefore listed as a category C pathogen. Hantavirus encodes an NP that plays essential roles both in RNP formation and

Crystal Structure of the Core Region of Hantavirus Nucleocapsid Protein Reveals the Mechanism for Ribonucleoprotein Complex Formation.

PubMed

Guo, Yu; Wang, Wenming; Sun, Yuna; Ma, Chao; Wang, Xu; Wang, Xin; Liu, Pi; Shen, Shu; Li, Baobin; Lin, Jianping; Deng, Fei; Wang, Hualin; Lou, Zhiyong

2016-01-15

Hantaviruses, which belong to the genus Hantavirus in the family Bunyaviridae, infect mammals, including humans, causing either hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS) in humans with high mortality. Hantavirus encodes a nucleocapsid protein (NP) to encapsidate the genome and form a ribonucleoprotein complex (RNP) together with viral polymerase. Here, we report the crystal structure of the core domains of NP (NPcore) encoded by Sin Nombre virus (SNV) and Andes virus (ANDV), which are two representative members that cause HCPS in the New World. The constructs of SNV and ANDV NPcore exclude the N- and C-terminal portions of full polypeptide to obtain stable proteins for crystallographic study. The structure features an N lobe and a C lobe to clamp RNA-binding crevice and exhibits two protruding extensions in both lobes. The positively charged residues located in the RNA-binding crevice play a key role in RNA binding and virus replication. We further demonstrated that the C-terminal helix and the linker region connecting the N-terminal coiled-coil domain and NPcore are essential for hantavirus NP oligomerization through contacts made with two adjacent protomers. Moreover, electron microscopy (EM) visualization of native RNPs extracted from the virions revealed that a monomer-sized NP-RNA complex is the building block of viral RNP. This work provides insight into the formation of hantavirus RNP and provides an understanding of the evolutionary connections that exist among bunyaviruses. Hantaviruses are distributed across a wide and increasing range of host reservoirs throughout the world. In particular, hantaviruses can be transmitted via aerosols of rodent excreta to humans or from human to human and cause HFRS and HCPS, with mortalities of 15% and 50%, respectively. Hantavirus is therefore listed as a category C pathogen. Hantavirus encodes an NP that plays essential roles both in RNP formation and in multiple

Hantavirus Prevalence in the IX Region of Chile

PubMed Central

Vial, Pablo C.; Castillo, Constanza H.; Godoy, Paula M.; Hjelle, Brian; Ferrés, Marcela G.

2003-01-01

An epidemiologic and seroprevalence survey was conducted (n=830) to assess proportion of persons exposed to hantavirus in IX Region Chile, which accounts for 25% of reported cases of hantavirus cardiopulmonary syndrome. This region has three geographic areas with different disease incidences and a high proportion of aboriginals. Serum samples were tested for immunoglobulin (Ig) G antibodies by enzyme-linked immunosorbent assay against Sin Nombre virus N antigen by strip immunoblot assay against Sin Nombre, Puumala, Río Mamoré, and Seoul N antigens. Samples from six patients were positive for IgG antibodies reactive with Andes virus; all patients lived in the Andes Mountains. Foresting was also associated with seropositivity; but not sex, age, race, rodent exposure, or farming activities. Exposure to hantavirus varies in different communities of IX Region. Absence of history of pneumonia or hospital admission in persons with specific IgG antibodies suggests that infection is clinically inapparent. PMID:12890323

Molecular method for the detection of Andes hantavirus infection: validation for clinical diagnostics

PubMed Central

Vial, Cecilia; Martinez-Valdebenito, Constanza; Rios, Susana; Martinez, Jessica; Vial, Pablo; Ferres, Marcela; Rivera, Juan Carlos; Perez, Ruth; Valdivieso, Francisca

2016-01-01

Hantavirus Cardiopulmonary Syndrome is a severe disease caused by exposure to New World hantaviruses. Early diagnosis is difficult due to the lack of specific initial symptoms. Anti-hantavirus antibodies are usually negative until late in the febrile prodrome or the beginning of cardiopulmonary phase while Andes hantavirus (ANDV) RNA genome can be detected before symptoms onset. We analyzed the effectiveness of RTqPCR as a diagnostic tool detecting ANDV-Sout genome in peripheral blood cells from 78 confirmed hantavirus patients and 166 negative controls. Our results indicate that RTqPCR had a low detection limit (~10 copies), with a specificity of 100% and a sensitivity of 94.9%. This suggests the potential for establishing RT-qPCR as the assay of choice for early diagnosis, promoting early effective care of patients and improve other important aspects of ANDV infection management, such as compliance of biosafety recommendations for health personnel in order to avoid nosocomial transmission. PMID:26508102

The post-pulmonary infarction syndrome.

PubMed

Sklaroff, H J

1979-12-01

Following pulmonary infarction, three patients developed the classical signs and symptoms of the Dressler syndrome associated with persistent left pleural effusion. Each responded dramatically to corticosteroid therapy. While the pathogenesis of this "Post-Pulmonary Infarction syndrome," like the Dressler syndrome, is unclear, the response to corticosteroid therapy is both dramatic and diagnostic and may spare the patient prolonged discomfort and unnecessary diagnostic procedures.

Discovery of hantaviruses and of the Hantavirus genus: personal and historical perspectives of the Presidents of the International Society of Hantaviruses.

PubMed

Lee, Ho Wang; Vaheri, Antti; Schmaljohn, Connie S

2014-07-17

We three authors, the two past presidents (HWL and AV) and the current president (CSS) of the International Society for Hantaviruses (ISH) have attended most of the nine International Conferences on HFRS, HPS and Hantaviruses (Table 1). These conferences have provided a forum for a synergistic group of clinicians, basic researchers, mammalogists, epidemiologists and ecologists to share their expertise and interests in all aspects of hantavirus research. Much of what is now hantavirus dogma was only conjecture when HWL organized the first conference in Seoul, Korea in 1989. Herein, we provide our reflections on key events in hantavirus research. As we come from distinct areas of the world and have had individual historical experiences, we certainly have our own geocentric opinions about the key events. Nevertheless, we agree that the discovery of hantaviruses has taken an interesting and unpredictable track to where we are today. Published by Elsevier B.V.

Modeling potential distribution of Oligoryzomys longicaudatus, the Andes virus (Genus: Hantavirus) reservoir, in Argentina.

PubMed

Andreo, Verónica; Glass, Gregory; Shields, Timothy; Provensal, Cecilia; Polop, Jaime

2011-09-01

We constructed a model to predict the potential distribution of Oligoryzomys longicaudatus, the reservoir of Andes virus (Genus: Hantavirus), in Argentina. We developed an extensive database of occurrence records from published studies and our own surveys and compared two methods to model the probability of O. longicaudatus presence; logistic regression and MaxEnt algorithm. The environmental variables used were tree, grass and bare soil cover from MODIS imagery and, altitude and 19 bioclimatic variables from WorldClim database. The models performances were evaluated and compared both by threshold dependent and independent measures. The best models included tree and grass cover, mean diurnal temperature range, and precipitation of the warmest and coldest seasons. The potential distribution maps for O. longicaudatus predicted the highest occurrence probabilities along the Andes range, from 32°S and narrowing southwards. They also predicted high probabilities for the south-central area of Argentina, reaching the Atlantic coast. The Hantavirus Pulmonary Syndrome cases coincided with mean occurrence probabilities of 95 and 77% for logistic and MaxEnt models, respectively. HPS transmission zones in Argentine Patagonia matched the areas with the highest probability of presence. Therefore, colilargos presence probability may provide an approximate risk of transmission and act as an early tool to guide control and prevention plans.

Isolation and characterization of microsatellite markers in Oligoryzomys longicaudatus (Muridae, Sigmodontinae, Oryzomini), the natural reservoir of genotype Andes hantavirus.

PubMed

González-Ittig, Raúl E; Salazar-Bravo, Jorge; Polop, Jaime J; Gardenal, Cristina N

2008-11-01

The rodent Oligoryzomys longicaudatus or long-tailed pygmy rice rat is the reservoir of the aetiological agent of the hantavirus pulmonary syndrome in southern Argentina and Chile. We characterize 11 polymorphic microsatellite loci which would be useful for studies on microgeographical population structure in the species. Amplification of these loci in 42 individuals from four natural populations revealed four to 21 alleles per locus, and values of observed heterozygosities ranging from 0.371 to 0.896. Cross-species amplifications showed that some of the primers designed may be useful for other species of the genus Oligoryzomys. © 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd.

Serological Survey of Hantavirus in Inhabitants from Tropical and Subtropical Areas of Brazil.

PubMed

Alves Morais, Felipe; Pereira, Alexandre; Santo Pietro Pereira, Aparecida; Lazaro Moreli, Marcos; Marcelo Aranha Camargo, Luís; Schiavo Nardi, Marcello; Farah Tófoli, Cristina; Araujo, Jansen; Mara Dutra, Lilia; Lopes Ometto, Tatiana; Hurtado, Renata; Carmona de Jesus Maués, Fábio; Zingano Hinke, Tiene; Jaber Mahmud, Sati; Correia Lima, Monica; Tadeu Moraes Figueiredo, Luiz; Luiz Durigon, Edison

2016-01-01

Brazil has reported more than 1,600 cases of hantavirus cardiopulmonary syndrome (HPS) since 1993, with a 39% rate of reported fatalities. Using a recombinant nucleocapsid protein of Araraquara virus, we performed ELISA to detect IgG antibodies against hantavirus in human sera. The aim of this study was to analyze hantavirus antibody levels in inhabitants from a tropical area (Amazon region) in Rondônia state and a subtropical (Atlantic Rain Forest) region in São Paulo state, Brazil. A total of 1,310 serum samples were obtained between 2003 and 2008 and tested by IgG-ELISA, and 82 samples (6.2%), of which 62 were from the tropical area (5.8%) and 20 from the subtropical area (8.3%), tested positive. Higher levels of hantavirus antibody were observed in inhabitants of the populous subtropical areas compared with those from the tropical areas in Brazil.

Daily Movements and Microhabitat Selection of Hantavirus Reservoirs and Other Sigmodontinae Rodent Species that Inhabit a Protected Natural Area of Argentina.

PubMed

Maroli, Malena; Vadell, María Victoria; Iglesias, Ayelén; Padula, Paula Julieta; Gómez Villafañe, Isabel Elisa

2015-09-01

Abundance, distribution, movement patterns, and habitat selection of a reservoir species influence the dispersal of zoonotic pathogens, and hence, the risk for humans. Movements and microhabitat use of rodent species, and their potential role in the transmission of hantavirus were studied in Otamendi Natural Reserve, Buenos Aires, Argentina. Movement estimators and qualitative characteristics of rodent paths were determined by means of a spool and line device method. Sampling was conducted during November and December 2011, and March, April, June, October, and December 2012. Forty-six Oxymycterus rufus, 41 Akodon azarae, 10 Scapteromys aquaticus and 5 Oligoryzomys flavescens were captured. Movement patterns and distances varied according to sex, habitat type, reproductive season, and body size among species. O. flavescens, reservoir of the etiologic agent of hantavirus pulmonary syndrome in the region, moved short distances, had the most linear paths and did not share paths with other species. A. azarae had an intermediate linearity index, its movements were longer in the highland grassland than in the lowland marsh and the salty grassland, and larger individuals traveled longer distances. O. rufus had the most tortuous paths and the males moved more during the non-breeding season. S. aquaticus movements were associated with habitat type with longer distances traveled in the lowland marsh than in the salty grassland. Hantavirus antibodies were detected in 20% of A. azarae and were not detected in any other species. Seropositive individuals were captured during the breeding season and 85% of them were males. A. azarae moved randomly and shared paths with all the other species, which could promote hantavirus spillover events.

Hantavirus Infection in the Republic of Georgia

DTIC Science & Technology

2009-09-01

causing hemor-rhagic fever with renal syndrome (HFRS) occur throughout most of Europe and Russia. The pathogenic hantaviruses detected in Europe and...on the strain of the infecting virus. Classic HFRS is characterized by fever , acute renal failure, hypotension, hemorrhage, and vascular leakage...Puumala virus typically induces a mild variant of HFRS (nephro- pathia epidemica) accompanied by high fever , headache, backache, and abdominal pain

Shared Ancestry between a Newfound Mole-Borne Hantavirus and Hantaviruses Harbored by Cricetid Rodents ▿†

PubMed Central

Kang, Hae Ji; Bennett, Shannon N.; Hope, Andrew G.; Cook, Joseph A.; Yanagihara, Richard

2011-01-01

Discovery of genetically distinct hantaviruses in multiple species of shrews (order Soricomorpha, family Soricidae) and moles (family Talpidae) contests the conventional view that rodents (order Rodentia, families Muridae and Cricetidae) are the principal reservoir hosts and suggests that the evolutionary history of hantaviruses is far more complex than previously hypothesized. We now report on Rockport virus (RKPV), a hantavirus identified in archival tissues of the eastern mole (Scalopus aquaticus) collected in Rockport, TX, in 1986. Pairwise comparison of the full-length S, M, and L genomic segments indicated moderately low sequence similarity between RKPV and other soricomorph-borne hantaviruses. Phylogenetic analyses, using maximum-likelihood and Bayesian methods, showed that RKPV shared a most recent common ancestor with cricetid-rodent-borne hantaviruses. Distributed widely across the eastern United States, the fossorial eastern mole is sympatric and syntopic with cricetid rodents known to harbor hantaviruses, raising the possibility of host-switching events in the distant past. Our findings warrant more-detailed investigations on the dynamics of spillover and cross-species transmission of present-day hantaviruses within communities of rodents and moles. PMID:21632770

Characterization of Puumala hantavirus in bank voles from two regions in the Netherlands where human cases occurred.

PubMed

de Vries, A; Vennema, H; Bekker, D L; Maas, M; Adema, J; Opsteegh, M; van der Giessen, J W B; Reusken, C B E M

2016-07-01

Puumala hantavirus (PUUV) is the most common and widespread hantavirus in Europe and is associated with a mild form of haemorrhagic fever with renal syndrome in humans, called nephropathia epidemica. This study presents the molecular characterization of PUUV circulating in bank voles in two regions of the Netherlands. Most human cases of hantavirus infection are from these two regions. Phylogenetic analysis of the (partial) S, M and L-segments indicated that the Dutch strains belong to the CE lineage, which includes PUUV strains from France, Germany and Belgium. We have identified two distinct groups of PUUV, corresponding with their geographic origin and with adjoining regions in neighbouring countries.

Pulmonary hypoplasia in Jarcho-Levin syndrome.

PubMed

Rodríguez, Luis M; García-García, Inés; Correa-Rivas, María S; García-Fragoso, Lourdes

2004-03-01

Jarcho-Levin syndrome, also known as spondylothoracic dysplasia and characterized by short trunk dwarfism, "crab-like" rib cage, with ribs and vertebral defects; it is not uncommon in Puerto Ricans. Many patients die in early infancy due to respiratory compromise associated to lung restriction and the reported cases emphasize mostly the skeletal malformations associated to the syndrome. We report the autopsy findings in a newborn with isolated Jarcho-Levin syndrome emphasizing pulmonary pathology. He was a pre-term male who died of respiratory failure at three hours old and, autopsy findings confirmed the clinical diagnosis. Internal examination showed hypoplastic lungs with normal lobation. The histological structure appeared normal and relatively mature; the diaphragm showed eventration and unilateral absence of musculature. This case shows the worst spectum of the Jarcho-Levin syndrome: pulmonary hypoplasia not compatible with extrauterine life. Since thoracic restriction is present during the fetal period, the degree of pulmonary hypoplasia probably defines survival beyond the neonatal period.

Pulmonary hypertension associated with thalassemia syndromes

PubMed Central

Fraidenburg, Dustin R.; Machado, Roberto F.

2016-01-01

Chronic hemolytic anemia has increasingly been identified as an important risk factor for the development of pulmonary hypertension. Within the thalassemia syndromes, there are multiple mechanisms, both distinct and overlapping, by which pulmonary hypertension develops and that differ among β-thalassemia major or intermedia patients. Pulmonary hypertension in β-thalassemia major correlates with the severity of hemolysis, yet in patients whose disease is well treated with chronic transfusion therapy, the development of pulmonary hypertension can be related to cardiac dysfunction and the subsequent toxic effects of iron overload rather than hemolysis. β-thalassemia intermedia, on the other hand, has a higher incidence of pulmonary hypertension owing to the low level of hemolysis that exists over years without the requirement for frequent transfusions, while splenectomy is shown to play an important role in both types. Standard therapies such as chronic transfusion have been shown to mitigate pulmonary hypertension, and appropriate chelation therapy can avoid the toxic effects of iron overload, yet is not indicated in many patients. Limited evidence exists for the use of pulmonary vasodilators or other therapies, such as l-carnitine, to treat pulmonary hypertension associated with thalassemia. Here we review the most recent findings regarding the pathogenic mechanisms, epidemiology, presentation, diagnosis, and treatment of pulmonary hypertension in thalassemia syndromes. PMID:27008311

Evidence of human hantavirus infection and zoonotic investigation of hantavirus prevalence in rodents in western Java, Indonesia.

PubMed

Kosasih, Herman; Ibrahim, Ima Nurisa; Wicaksana, Rudi; Alisjahbana, Bachti; Hoo, Yumilia; Yo, Iing H; Antonjaya, Ungke; Widjaja, Susana; Winoto, Imelda; Williams, Maya; Blair, Patrick J

2011-06-01

During febrile surveillance in the western Java City of Bandung, Indonesia, a patient with clinical symptoms consistent with hantavirus infection was found to have elevated titers of hantavirus-specific immunoglobulin M (IgM) and IgG antibodies. A subsequent epizoological investigation demonstrated a higher prevalence of hantavirus IgG antibodies in rodents trapped in the vicinity of the patient's home compared with rodents from a control area (13.2% vs. 4.7%, p = 0.036). The Old World Seoul hantavirus was detected by reverse transcriptase-polymerase chain reaction in the organs of 71% of the seropositive rodents tested. This is the first report of a Seoul virus infection in Indonesia supported by clinical, serological, and epizoological evidences. These findings suggest that hantavirus infection should be on the clinical differential diagnosis when acutely ill febrile patients report for care in western Java.

Phylogenetic Relationship of Necoclí Virus to Other South American Hantaviruses (Bunyaviridae: Hantavirus).

PubMed

Montoya-Ruiz, Carolina; Cajimat, Maria N B; Milazzo, Mary Louise; Diaz, Francisco J; Rodas, Juan David; Valbuena, Gustavo; Fulhorst, Charles F

2015-07-01

The results of a previous study suggested that Cherrie's cane rat (Zygodontomys cherriei) is the principal host of Necoclí virus (family Bunyaviridae, genus Hantavirus) in Colombia. Bayesian analyses of complete nucleocapsid protein gene sequences and complete glycoprotein precursor gene sequences in this study confirmed that Necoclí virus is phylogenetically closely related to Maporal virus, which is principally associated with the delicate pygmy rice rat (Oligoryzomys delicatus) in western Venezuela. In pairwise comparisons, nonidentities between the complete amino acid sequence of the nucleocapsid protein of Necoclí virus and the complete amino acid sequences of the nucleocapsid proteins of other hantaviruses were ≥8.7%. Likewise, nonidentities between the complete amino acid sequence of the glycoprotein precursor of Necoclí virus and the complete amino acid sequences of the glycoprotein precursors of other hantaviruses were ≥11.7%. Collectively, the unique association of Necoclí virus with Z. cherriei in Colombia, results of the Bayesian analyses of complete nucleocapsid protein gene sequences and complete glycoprotein precursor gene sequences, and results of the pairwise comparisons of amino acid sequences strongly support the notion that Necoclí virus represents a novel species in the genus Hantavirus. Further work is needed to determine whether Calabazo virus (a hantavirus associated with Z. brevicauda cherriei in Panama) and Necoclí virus are conspecific.

Person-to-Person Household and Nosocomial Transmission of Andes Hantavirus, Southern Chile, 2011

PubMed Central

Martinez-Valdebenito, Constanza; Calvo, Mario; Vial, Cecilia; Mansilla, Rita; Marco, Claudia; Palma, R. Eduardo; Vial, Pablo A.; Valdivieso, Francisca; Mertz, Gregory

2014-01-01

Andes hantavirus (ANDV) causes hantavirus cardiopulmonary syndrome in Chile and is the only hantavirus for which person-to-person transmission has been proven. We describe an outbreak of 5 human cases of ANDV infection in which symptoms developed in 2 household contacts and 2 health care workers after exposure to the index case-patient. Results of an epidemiologic investigation and sequence analysis of the virus isolates support person-to-person transmission of ANDV for the 4 secondary case-patients, including nosocomial transmission for the 2 health care workers. Health care personnel who have direct contact with ANDV case-patients or their body fluids should take precautions to prevent transmission of the virus. In addition, because the incubation period of ANDV after environmental exposure is longer than that for person-to-person exposure, all persons exposed to a confirmed ANDV case-patient or with possible environmental exposure to the virus should be monitored for 42 days for clinical symptoms. PMID:25272189

Serologic evidence for human hantavirus infection in Peru.

PubMed

Castillo Oré, Roger M; Forshey, Brett M; Huaman, Alfredo; Villaran, Manuel V; Long, Kanya C; Kochel, Tadeusz J; Guevara, Carolina; Montgomery, Joel M; Alvarez, Carlos A; Vilcarromero, Stalin; Morrison, Amy C; Halsey, Eric S

2012-08-01

While human illness associated with hantavirus infection has been documented in many countries of South America, evidence for hantavirus transmission in Peru has been limited to the isolation of Rio Mamore virus from a pigmy mouse rat (Oligoryzomys microtis) in the Amazon city of Iquitos. To address the possibility of human hantavirus exposure in the region, we screened febrile patients reporting to health clinics in Iquitos from 2007 to 2010 for serological evidence of recent hantavirus infection. In addition, we conducted a serological survey for hantavirus-reactive IgG among healthy participants residing in Iquitos and rural areas surrounding the city. Through the febrile surveillance study, we identified 15 participants (0.3%; 15/5174) with IgM reactive to hantavirus (Andes virus) antigen, all with relatively mild, self-limited illness. From the cross-sectional serosurvey we found that 1.7% (36/2063) of residents of the Iquitos area had serum IgG reactive to one or more hantaviruses, with a higher prevalence in the urban population (2.2%, compared to 1.1% in rural areas). These results suggest that human infection with hantavirus has occurred in Peru.

Hantavirus reservoir Oligoryzomys longicaudatus spatial distribution sensitivity to climate change scenarios in Argentine Patagonia

PubMed Central

Carbajo, Aníbal E; Vera, Carolina; González, Paula LM

2009-01-01

Background Oligoryzomys longicaudatus (colilargo) is the rodent responsible for hantavirus pulmonary syndrome (HPS) in Argentine Patagonia. In past decades (1967–1998), trends of precipitation reduction and surface air temperature increase have been observed in western Patagonia. We explore how the potential distribution of the hantavirus reservoir would change under different climate change scenarios based on the observed trends. Methods Four scenarios of potential climate change were constructed using temperature and precipitation changes observed in Argentine Patagonia between 1967 and 1998: Scenario 1 assumed no change in precipitation but a temperature trend as observed; scenario 2 assumed no changes in temperature but a precipitation trend as observed; Scenario 3 included changes in both temperature and precipitation trends as observed; Scenario 4 assumed changes in both temperature and precipitation trends as observed but doubled. We used a validated spatial distribution model of O. longicaudatus as a function of temperature and precipitation. From the model probability of the rodent presence was calculated for each scenario. Results If changes in precipitation follow previous trends, the probability of the colilargo presence would fall in the HPS transmission zone of northern Patagonia. If temperature and precipitation trends remain at current levels for 60 years or double in the future 30 years, the probability of the rodent presence and the associated total area of potential distribution would diminish throughout Patagonia; the areas of potential distribution for colilargos would shift eastwards. These results suggest that future changes in Patagonia climate may lower transmission risk through a reduction in the potential distribution of the rodent reservoir. Conclusion According to our model the rates of temperature and precipitation changes observed between 1967 and 1998 may produce significant changes in the rodent distribution in an equivalent

Hantavirus Pulmonary Syndrome (HPS)

MedlinePlus

... States, in an area shared by Arizona, New Mexico, Colorado and Utah known as “The Four Corners”. ... breath was rushed to a hospital in New Mexico and died very rapidly. Severe HPS. Image courtesy ...

Using Geographic Information System-based Ecologic Niche Models to Forecast the Risk of Hantavirus Infection in Shandong Province, China

PubMed Central

Wei, Lan; Qian, Quan; Wang, Zhi-Qiang; Glass, Gregory E.; Song, Shao-Xia; Zhang, Wen-Yi; Li, Xiu-Jun; Yang, Hong; Wang, Xian-Jun; Fang, Li-Qun; Cao, Wu-Chun

2011-01-01

Hemorrhagic fever with renal syndrome (HFRS) is an important public health problem in Shandong Province, China. In this study, we combined ecologic niche modeling with geographic information systems (GIS) and remote sensing techniques to identify the risk factors and affected areas of hantavirus infections in rodent hosts. Land cover and elevation were found to be closely associated with the presence of hantavirus-infected rodent hosts. The averaged area under the receiver operating characteristic curve was 0.864, implying good performance. The predicted risk maps based on the model were validated both by the hantavirus-infected rodents' distribution and HFRS human case localities with a good fit. These findings have the applications for targeting control and prevention efforts. PMID:21363991

Old World Hantaviruses in Rodents in New Orleans, Louisiana

PubMed Central

Cross, Robert W.; Waffa, Bradley; Freeman, Ashley; Riegel, Claudia; Moses, Lina M.; Bennett, Andrew; Safronetz, David; Fischer, Elizabeth R.; Feldmann, Heinz; Voss, Thomas G.; Bausch, Daniel G.

2014-01-01

Seoul virus, an Old World hantavirus, is maintained in brown rats and causes a mild form of hemorrhagic fever with renal syndrome (HFRS) in humans. We captured rodents in New Orleans, Louisiana and tested them for the presence of Old World hantaviruses by reverse transcription polymerase chain reaction (RT-PCR) with sequencing, cell culture, and electron microscopy; 6 (3.4%) of 178 rodents captured—all brown rats—were positive for a Seoul virus variant previously coined Tchoupitoulas virus, which was noted in rodents in New Orleans in the 1980s. The finding of Tchoupitoulas virus in New Orleans over 25 years since its first discovery suggests stable endemicity in the city. Although the degree to which this virus causes human infection and disease remains unknown, repeated demonstration of Seoul virus in rodent populations, recent cases of laboratory-confirmed HFRS in some US cities, and a possible link with hypertensive renal disease warrant additional investigation in both rodents and humans. PMID:24639295

Old World hantaviruses in rodents in New Orleans, Louisiana.

PubMed

Cross, Robert W; Waffa, Bradley; Freeman, Ashley; Riegel, Claudia; Moses, Lina M; Bennett, Andrew; Safronetz, David; Fischer, Elizabeth R; Feldmann, Heinz; Voss, Thomas G; Bausch, Daniel G

2014-05-01

Seoul virus, an Old World hantavirus, is maintained in brown rats and causes a mild form of hemorrhagic fever with renal syndrome (HFRS) in humans. We captured rodents in New Orleans, Louisiana and tested them for the presence of Old World hantaviruses by reverse transcription polymerase chain reaction (RT-PCR) with sequencing, cell culture, and electron microscopy; 6 (3.4%) of 178 rodents captured--all brown rats--were positive for a Seoul virus variant previously coined Tchoupitoulas virus, which was noted in rodents in New Orleans in the 1980s. The finding of Tchoupitoulas virus in New Orleans over 25 years since its first discovery suggests stable endemicity in the city. Although the degree to which this virus causes human infection and disease remains unknown, repeated demonstration of Seoul virus in rodent populations, recent cases of laboratory-confirmed HFRS in some US cities, and a possible link with hypertensive renal disease warrant additional investigation in both rodents and humans.

Muju virus, a novel hantavirus harboured by the arvicolid rodent Myodes regulus in Korea

PubMed Central

Song, Ki-Joon; Baek, Luck Ju; Moon, Sungsil; Ha, Si Jung; Kim, Sang Hyun; Park, Kwang Sook; Klein, Terry A.; Sames, William; Kim, Heung-Chul; Lee, John S.; Yanagihara, Richard; Song, Jin-Won

2008-01-01

Acute-phase sera from >5 % of cases of haemorrhagic fever with renal syndrome occurring annually in Korea have been found to exhibit a fourfold or higher antibody titre to Puumala virus (PUUV) than to Hantaan virus (HTNV) by double-sandwich IgM ELISA, suggesting the existence of a PUUV-related hantavirus. Based on the phylogenetic relationships among arvicolid rodents, the royal vole (Myodes regulus) was targeted as a likely reservoir host of hantavirus. Using RT-PCR, a genetically distinct hantavirus, designated Muju virus (MUJV), was detected in lung tissue of royal voles, captured in widely separated geographical regions in Korea during 1996–2007. Pairwise analysis of the full-length S (1857 nt) and M (3634 nt) segments of MUJV indicated approximately 77 % sequence similarity with PUUV. At the amino acid level, MUJV differed from PUUV by 5.5–6.9 % (nucleocapsid) and 10.0–11.6 % (Gn and Gc envelope glycoproteins). Interstrain variation of MUJV sequences from royal voles captured in different regions suggested geographic-specific clustering. Neutralizing antibody titres against PUUV were two- to sixfold higher than to HTNV in sera of MUJV-infected Myodes regulus. Although virus isolation attempts were unsuccessful, the collective data indicate that MUJV is a distinct hantavirus species. PMID:17947538

Long-term persistence of anti-hantavirus antibodies in sera of patients undergoing hemorrhagic fever with renal syndrome and subjects vaccinated against the disease.

PubMed

Zheng, Yuan; Wei, Jing; Zhou, Bu-Yu; Xu, Yi; Dong, Jian-Hua; Guan, Lu-Yuan; Ma, Ping; Yu, Peng-Bo; Wang, Jing-Jun

2016-04-01

Background China has the highest prevalence of hemorrhagic fever with renal syndrome (HFRS) and accounts for 90% of the total cases worldwide. However, the long-term persistence of anti-hantavirus antibodies in sera of patients with HFRS and subjects vaccinated against the disease remains unclear. The aim of the present study was to investigate the prevalence of anti-hantavirus IgG antibodies in sera of patients with prior HFRS, versus subjects vaccinated against the disease and controls in Shaanxi, China. Methods Six hundred individuals were included in this study. We quantified anti-hantavirus IgG antibodies in HFRS patients (n = 100), vaccinees (n = 200), controls from endemic regions (n = 200), and controls from non-endemic regions (n = 100) in China. Results The median optical density (OD) values (range) were 0.803 (0.008-1.813), 0.075 (0.004-1.565), 0.026 (0-1.179), and 0.015 (0.009-0.118) for HFRS patients, vaccinated subjects, endemic controls, and non-endemic controls, respectively. There was a strikingly significant difference between the HFRS group and each non-HFRS group (p < 0.001). The vaccinated subjects were also significantly different from the endemic controls. The time since the acute phase was correlated with the OD values of the HFRS patients. Conclusions Our study suggests that HFRS patients gain long-lasting protection and that vaccination may be an effective way to stimulate antibody production.

Urbanization prolongs hantavirus epidemics in cities.

PubMed

Tian, Huaiyu; Hu, Shixiong; Cazelles, Bernard; Chowell, Gerardo; Gao, Lidong; Laine, Marko; Li, Yapin; Yang, Huisuo; Li, Yidan; Yang, Qiqi; Tong, Xin; Huang, Ru; Bjornstad, Ottar N; Xiao, Hong; Stenseth, Nils Chr

2018-05-01

Urbanization and rural-urban migration are two factors driving global patterns of disease and mortality. There is significant concern about their potential impact on disease burden and the effectiveness of current control approaches. Few attempts have been made to increase our understanding of the relationship between urbanization and disease dynamics, although it is generally believed that urban living has contributed to reductions in communicable disease burden in industrialized countries. To investigate this relationship, we carried out spatiotemporal analyses using a 48-year-long dataset of hemorrhagic fever with renal syndrome incidence (HFRS; mainly caused by two serotypes of hantavirus in China: Hantaan virus and Seoul virus) and population movements in an important endemic area of south China during the period 1963-2010. Our findings indicate that epidemics coincide with urbanization, geographic expansion, and migrant movement over time. We found a biphasic inverted U-shaped relationship between HFRS incidence and urbanization, with various endemic turning points associated with economic growth rates in cities. Our results revealed the interrelatedness of urbanization, migration, and hantavirus epidemiology, potentially explaining why urbanizing cities with high economic growth exhibit extended epidemics. Our results also highlight contrasting effects of urbanization on zoonotic disease outbreaks during periods of economic development in China. Copyright © 2018 the Author(s). Published by PNAS.

Urbanization prolongs hantavirus epidemics in cities

PubMed Central

Tian, Huaiyu; Hu, Shixiong; Chowell, Gerardo; Gao, Lidong; Li, Yapin; Yang, Huisuo; Li, Yidan; Yang, Qiqi; Tong, Xin; Huang, Ru; Bjornstad, Ottar N.; Xiao, Hong; Stenseth, Nils Chr.

2018-01-01

Urbanization and rural–urban migration are two factors driving global patterns of disease and mortality. There is significant concern about their potential impact on disease burden and the effectiveness of current control approaches. Few attempts have been made to increase our understanding of the relationship between urbanization and disease dynamics, although it is generally believed that urban living has contributed to reductions in communicable disease burden in industrialized countries. To investigate this relationship, we carried out spatiotemporal analyses using a 48-year-long dataset of hemorrhagic fever with renal syndrome incidence (HFRS; mainly caused by two serotypes of hantavirus in China: Hantaan virus and Seoul virus) and population movements in an important endemic area of south China during the period 1963–2010. Our findings indicate that epidemics coincide with urbanization, geographic expansion, and migrant movement over time. We found a biphasic inverted U-shaped relationship between HFRS incidence and urbanization, with various endemic turning points associated with economic growth rates in cities. Our results revealed the interrelatedness of urbanization, migration, and hantavirus epidemiology, potentially explaining why urbanizing cities with high economic growth exhibit extended epidemics. Our results also highlight contrasting effects of urbanization on zoonotic disease outbreaks during periods of economic development in China. PMID:29666240

High prevalence of Seoul hantavirus in a breeding colony of pet rats.

PubMed

McELHINNEY, L M; Marston, D A; Pounder, K C; Goharriz, H; Wise, E L; Verner-Carlsson, J; Jennings, D; Johnson, N; Civello, A; Nunez, A; Brooks, T; Breed, A C; Lawes, J; Lundkvist, Å; Featherstone, C A; Fooks, A R

2017-11-01

As part of further investigations into three linked haemorrhagic fever with renal syndrome (HFRS) cases in Wales and England, 21 rats from a breeding colony in Cherwell, and three rats from a household in Cheltenham were screened for hantavirus. Hantavirus RNA was detected in either the lungs and/or kidney of 17/21 (81%) of the Cherwell rats tested, higher than previously detected by blood testing alone (7/21, 33%), and in the kidneys of all three Cheltenham rats. The partial L gene sequences obtained from 10 of the Cherwell rats and the three Cheltenham rats were identical to each other and the previously reported UK Cherwell strain. Seoul hantavirus (SEOV) RNA was detected in the heart, kidney, lung, salivary gland and spleen (but not in the liver) of an individual rat from the Cherwell colony suspected of being the source of SEOV. Serum from 20/20 of the Cherwell rats and two associated HFRS cases had high levels of SEOV-specific antibodies (by virus neutralisation). The high prevalence of SEOV in both sites and the moderately severe disease in the pet rat owners suggest that SEOV in pet rats poses a greater public health risk than previously considered.

[Study on the genetic difference of SEO type Hantaviruses].

PubMed

Zhang, X; Zhou, S; Wang, H; Hu, J; Guan, Z; Liu, H

2000-10-01

To understand the genetic type of Hantaviruses and the difference between them caused by rodents in Beijing and to furhter explore the source of the infectious factors. Hantavirus RNA, isolated from lungs of rodents captured in Beijing and positive with Hantavirus antigens with frozen sectioning and Immunofluorescent assay, were reverse-transcribed and amplified with PCR with Hantavirus-specific primers. Five of the PCR amplifications were discovered and sequenced with 300 bp sequence data of M segments (from 2003 - 2302nt according cDNA of seoul 8039 strain). Nucleotide sequence homology showed that they were sequences of SEO-type Hantavirus. Compared with SEO type Hantavirus, the nucleotide sequence homology of these samples was more than 94% while the homology of amonia acid sequence was more than 98%. When compared with HNT type Hantavirus, the homology of nucleotide sequence became less than 72% with the homology of amonia acid sequence less than 81%. Similar to other Hantavirus of SEO type, their nucleotide sequences and deduced amino acid sequences were highly preserved. Phylogenetic tree analysis showed that the five viruses could be divided into at least 4 branches. It was quite likely that there were at least two sub-type SEO viruses with 4 branches that were circulating in Beijing.

Earlier Pulmonary Valve Replacement in Down Syndrome Patients Following Tetralogy of Fallot Repair.

PubMed

Sullivan, Rachel T; Frommelt, Peter C; Hill, Garick D

2017-08-01

The association between Down syndrome and pulmonary hypertension could contribute to more severe pulmonary regurgitation after tetralogy of Fallot repair and possibly earlier pulmonary valve replacement. We compared cardiac magnetic resonance measures of pulmonary regurgitation and right ventricular dilation as well as timing of pulmonary valve replacement between those with and without Down syndrome after tetralogy of Fallot repair. Review of our surgical database from 2000 to 2015 identified patients with tetralogy of Fallot with pulmonary stenosis. Those with Down syndrome were compared to those without. The primary outcome of interest was time from repair to pulmonary valve replacement. Secondary outcomes included pulmonary regurgitation and indexed right ventricular volume on cardiac magnetic resonance imaging. The cohort of 284 patients included 35 (12%) with Down syndrome. Transannular patch repair was performed in 210 (74%). Down syndrome showed greater degree of pulmonary regurgitation (55 ± 14 vs. 37 ± 16%, p = 0.01) without a significantly greater rate of right ventricular dilation (p = 0.09). In multivariable analysis, Down syndrome (HR 2.3, 95% CI 1.2-4.5, p = 0.02) and transannular patch repair (HR 5.5, 95% CI 1.7-17.6, p = 0.004) were significant risk factors for valve replacement. Those with Down syndrome had significantly lower freedom from valve replacement (p = 0.03). Down syndrome is associated with an increased degree of pulmonary regurgitation and earlier pulmonary valve replacement after tetralogy of Fallot repair. These patients require earlier assessment by cardiac magnetic resonance imaging to determine timing of pulmonary valve replacement and evaluation for and treatment of preventable causes of pulmonary hypertension.

Heterotaxy syndrome with severe pulmonary hypertension in an adult.

PubMed

Brandenburg, Vincent M; Krueger, Stefan; Haage, Patrick; Mertens, Peter; Riehl, Jochen

2002-05-01

Heterotaxy syndrome is a rare clinical entity in adults, characterized by situs ambiguus, congenital heart defects, and splenic malformations. We report the case of an adult with heterotaxy syndrome (including situs ambiguus, bilateral superior vena cava, hypoplastic right-sided spleen and portosystemic shunts) presenting with dyspnea due to severe pulmonary hypertension. Vasodilatory therapy was initiated, leading to marked reduction of clinical symptoms. This case exhibits 2 particular and partially novel features: primary diagnosis of heterotaxy syndrome may be delayed until adulthood, and heterotaxy syndrome may be associated with pulmonary hypertension, possibly on the basis of longstanding portosystemic shunts.

Pulmonary vein stenosis in patients with Smith-Lemli-Opitz syndrome.

PubMed

Prosnitz, Aaron R; Leopold, Jane; Irons, Mira; Jenkins, Kathy; Roberts, Amy E

2017-07-01

To describe a group of children with co-incident pulmonary vein stenosis and Smith-Lemli-Opitz syndrome and to generate hypotheses as to the shared pathogenesis of these disorders. Retrospective case series. Five subjects in a pulmonary vein stenosis cohort of 170 subjects were diagnosed with Smith-Lemli-Opitz syndrome soon after birth. All five cases were diagnosed with Smith-Lemli-Opitz syndrome within 6 weeks of life, with no family history of either disorder. All cases had pathologically elevated 7-dehydrocholesterol levels and two of the five cases had previously reported pathogenic 7-dehydrocholesterol reductase mutations. Smith-Lemli-Opitz syndrome severity scores ranged from mild to classical (2-7). Gestational age at birth ranged from 35 to 39 weeks. Four of the cases were male by karyotype. Pulmonary vein stenosis was diagnosed in all cases within 2 months of life, earlier than most published cohorts. All cases progressed to bilateral disease and three cases developed atresia of at least one vein. Despite catheter and surgical interventions, all subjects' pulmonary vein stenosis rapidly recurred and progressed. Three of the subjects died, at 2 months, 3 months, and 11 months. Survival at 16 months after diagnosis was 43%. Patients with pulmonary vein stenosis who have a suggestive syndromic presentation should be screened for Smith-Lemli-Opitz syndrome with easily obtainable serum sterol tests. Echocardiograms should be obtained in all newly diagnosed patients with Smith-Lemli-Opitz syndrome, with a low threshold for repeating the study if new respiratory symptoms of uncertain etiology arise. Further studies into the pathophysiology of pulmonary vein stenosis should consider the role of cholesterol-based signaling pathways in the promotion of intimal proliferation. © 2017 Wiley Periodicals, Inc.

Knowledge, attitudes, and practices regarding hantavirus disease and acceptance of a vaccine trial in rural communities of southern Chile.

PubMed

Valdivieso, Francisca; Gonzalez, Claudia; Najera, Manuel; Olea, Andrea; Cuiza, Analia; Aguilera, Ximena; Mertz, Gregory

2017-04-03

Andes hantavirus cardiopulmonary syndrome, transmitted by Oligoryzomys longicaudatus, has no approved treatment, a case fatality rate of 35%, and documented person-to-person transmission. An Andes vaccine, highly needed for prevention, is in development. We aimed to evaluate knowledge, attitudes and practices (KAP) regarding hantavirus disease and willingness to participate in a future Andes vaccine trials through a cross sectional face-to-face oral survey of a randomly selected adult sample from 2 rural communes in southern Chile. Human subjects approval was obtained from our institutional IRBs, and participants signed informed consent. We enrolled 319 subjects from Corral and 321 from Curarrehue; 98% had heard about hantavirus disease and its reservoir but only half knew about transmission, symptoms and prevention. Participants fear the disease but are only partially aware of their own risk. One third of participants reported presence of rodents inside their homes. Despite moderate confidence in their health system, most subjects perceived vaccines as beneficial, and 93% would accept an approved hantavirus vaccine. Half would agree to participate in a vaccine trial and 29% would allow their children to participate. Motivations to participate were mainly altruistic, while risk perception was the main reason for declining. Knowledge about hantavirus disease and prevention practices require reinforcement, and a vaccine trial seems feasible in these populations.

[Familial pulmonary fibrosis in 2 Mexican sisters with Hermansky-Pudlak syndrome].

PubMed

Zamora, Ana C; Alonso-Martínez, Delfino; Barrera, Lourdes; Mendoza, Felipe; Gaxiola, Miguel; Carrillo, Guillermo

2009-08-01

Hermansky-Pudlak syndrome is an autosomal recessive disorder commonly found in individuals of Puerto Rican ancestry. We present 2 cases of familial pulmonary fibrosis in 2 Mexican sisters with Hermansky-Pudlak syndrome. Pulmonary fibrosis was biopsy-proven in 1 of the patients. This report shows that Hermansky-Pudlak syndrome may occur in individuals of Mexican ancestry.

Andes hantavirus variant in rodents, southern Amazon Basin, Peru.

PubMed

Razuri, Hugo; Tokarz, Rafal; Ghersi, Bruno M; Salmon-Mulanovich, Gabriela; Guezala, M Claudia; Albujar, Christian; Mendoza, A Patricia; Tinoco, Yeny O; Cruz, Christopher; Silva, Maria; Vasquez, Alicia; Pacheco, Víctor; Ströher, Ute; Guerrero, Lisa Wiggleton; Cannon, Deborah; Nichol, Stuart T; Hirschberg, David L; Lipkin, W Ian; Bausch, Daniel G; Montgomery, Joel M

2014-02-01

We investigated hantaviruses in rodents in the southern Amazon Basin of Peru and identified an Andes virus variant from Neacomys spinosus mice. This finding extends the known range of this virus in South America and the range of recognized hantaviruses in Peru. Further studies of the epizoology of hantaviruses in this region are warranted.

Climate change and sugarcane expansion increase Hantavirus infection risk.

PubMed

Prist, Paula Ribeiro; Uriarte, María; Fernandes, Katia; Metzger, Jean Paul

2017-07-01

Hantavirus Cardiopulmonary Syndrome (HCPS) is a disease caused by Hantavirus, which is highly virulent for humans. High temperatures and conversion of native vegetation to agriculture, particularly sugarcane cultivation can alter abundance of rodent generalist species that serve as the principal reservoir host for HCPS, but our understanding of the compound effects of land use and climate on HCPS incidence remains limited, particularly in tropical regions. Here we rely on a Bayesian model to fill this research gap and to predict the effects of sugarcane expansion and expected changes in temperature on Hantavirus infection risk in the state of São Paulo, Brazil. The sugarcane expansion scenario was based on historical data between 2000 and 2010 combined with an agro-environment zoning guideline for the sugar and ethanol industry. Future evolution of temperature anomalies was derived using 32 general circulation models from scenarios RCP4.5 and RCP8.5 (Representative greenhouse gases Concentration Pathways adopted by IPCC). Currently, the state of São Paulo has an average Hantavirus risk of 1.3%, with 6% of the 645 municipalities of the state being classified as high risk (HCPS risk ≥ 5%). Our results indicate that sugarcane expansion alone will increase average HCPS risk to 1.5%, placing 20% more people at HCPS risk. Temperature anomalies alone increase HCPS risk even more (1.6% for RCP4.5 and 1.7%, for RCP8.5), and place 31% and 34% more people at risk. Combined sugarcane and temperature increases led to the same predictions as scenarios that only included temperature. Our results demonstrate that climate change effects are likely to be more severe than those from sugarcane expansion. Forecasting disease is critical for the timely and efficient planning of operational control programs that can address the expected effects of sugarcane expansion and climate change on HCPS infection risk. The predicted spatial location of HCPS infection risks obtained here can be

Climate change and sugarcane expansion increase Hantavirus infection risk

PubMed Central

Uriarte, María; Fernandes, Katia; Metzger, Jean Paul

2017-01-01

Hantavirus Cardiopulmonary Syndrome (HCPS) is a disease caused by Hantavirus, which is highly virulent for humans. High temperatures and conversion of native vegetation to agriculture, particularly sugarcane cultivation can alter abundance of rodent generalist species that serve as the principal reservoir host for HCPS, but our understanding of the compound effects of land use and climate on HCPS incidence remains limited, particularly in tropical regions. Here we rely on a Bayesian model to fill this research gap and to predict the effects of sugarcane expansion and expected changes in temperature on Hantavirus infection risk in the state of São Paulo, Brazil. The sugarcane expansion scenario was based on historical data between 2000 and 2010 combined with an agro-environment zoning guideline for the sugar and ethanol industry. Future evolution of temperature anomalies was derived using 32 general circulation models from scenarios RCP4.5 and RCP8.5 (Representative greenhouse gases Concentration Pathways adopted by IPCC). Currently, the state of São Paulo has an average Hantavirus risk of 1.3%, with 6% of the 645 municipalities of the state being classified as high risk (HCPS risk ≥ 5%). Our results indicate that sugarcane expansion alone will increase average HCPS risk to 1.5%, placing 20% more people at HCPS risk. Temperature anomalies alone increase HCPS risk even more (1.6% for RCP4.5 and 1.7%, for RCP8.5), and place 31% and 34% more people at risk. Combined sugarcane and temperature increases led to the same predictions as scenarios that only included temperature. Our results demonstrate that climate change effects are likely to be more severe than those from sugarcane expansion. Forecasting disease is critical for the timely and efficient planning of operational control programs that can address the expected effects of sugarcane expansion and climate change on HCPS infection risk. The predicted spatial location of HCPS infection risks obtained here can be

Andes Hantavirus Variant in Rodents, Southern Amazon Basin, Peru

PubMed Central

Tokarz, Rafal; Ghersi, Bruno M.; Salmon-Mulanovich, Gabriela; Guezala, M. Claudia; Albujar, Christian; Mendoza, A. Patricia; Tinoco, Yeny O.; Cruz, Christopher; Silva, Maria; Vasquez, Alicia; Pacheco, Víctor; Ströher, Ute; Guerrero, Lisa Wiggleton; Cannon, Deborah; Nichol, Stuart T.; Hirschberg, David L.; Lipkin, W. Ian; Bausch, Daniel G.; Montgomery, Joel M.

2014-01-01

We investigated hantaviruses in rodents in the southern Amazon Basin of Peru and identified an Andes virus variant from Neacomys spinosus mice. This finding extends the known range of this virus in South America and the range of recognized hantaviruses in Peru. Further studies of the epizoology of hantaviruses in this region are warranted. PMID:24447689

Efficacy and safety of oral sildenafil in children with Down syndrome and pulmonary hypertension.

PubMed

Beghetti, Maurice; Rudzinski, Andrzej; Zhang, Min

2017-07-04

Despite the increased risk for pulmonary hypertension in children with Down syndrome, the response to treatment with targeted therapies for pulmonary hypertension in these patients is not well characterized. The Sildenafil in Treatment-naive children, Aged 1-17 years, with pulmonary arterial hypertension (STARTS-1) trial was a dose-ranging study of the short-term efficacy and safety of oral sildenafil in children with pulmonary arterial hypertension. We assessed the safety and efficacy of oral sildenafil in children with Down syndrome and pulmonary arterial hypertension. This was a post-hoc analysis of children with Down syndrome and pulmonary arterial hypertension enrolled in the STARTS-1 trial. Mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance index (PVRI), and cardiac index (CI) were assessed at baseline and following 16 weeks of treatment with sildenafil. Of 234 patients randomized and treated in the STARTS-1 trial, 48 (20.5%) had Down syndrome. Although sildenafil produced dose-related reductions in PVRI and mPAP, compared with placebo, in non-Down syndrome patients and children developmentally able to exercise, this was not satisfactorily marked in patients with Down syndrome. The dose-related reductions in PVRI, compared with placebo, occurred in all subgroups, with the exception of the Down syndrome subgroup. Sildenafil appeared to be well tolerated in the Down syndrome subpopulation and the most frequently reported AEs were similar to those reported for the entire STARTS-1 population. Sildenafil treatment for 16 weeks had no effect on PVRI or mPAP in children with Down syndrome and pulmonary arterial hypertension. The results suggest that children with Down syndrome may be less responsive to sildenafil for pulmonary arterial hypertension, but the incomplete work-up for the etiology of pulmonary arterial hypertension may have introduced a potential bias. Study received, September 8, 2005 (retrospectively registered); Study start

Rapidly progressive pulmonary veno-occlusive disease in an infant with Down syndrome.

PubMed

Muneuchi, Jun; Oda, Shinichiro; Shimizu, Daisuke

2017-09-01

A 4-month-old girl with Down syndrome showed unexpected deterioration of pulmonary hypertension. Despite aggressive pulmonary vasodilation therapy, the patient died at 5 months of age. Lung autopsy showed that the pulmonary veins were obliterated by intimal fibrous thickening, and the media of the veins was arterialised with an increase in elastic fibres. Pulmonary veno-occlusive disease should be considered in the management of individuals with Down syndrome.

Dobrava Hantavirus Infection Complicated by Panhypopituitarism, Istanbul, Turkey, 2010

PubMed Central

Hofmann, Jörg; Canpolat, Alper Tunga; Türk, Ali; Ettinger, Jakob; Atmaca, Deniz; Akyar, Işın; Yücel, Serap; Arıkan, Ender; Uyar, Yavuz; Çağlayık, Dilek Y.; Kocagöz, Ayşe Sesin; Kaya, Ayşin; Kruger, Detlev H.

2012-01-01

We identified Dobrava-Belgrade virus infection in Turkey (from a strain related to hantavirus strains from nearby countries) in a patient who had severe symptoms leading to panhypopituitarism, but no known risk for hantavirus. Our findings emphasize the need for increased awareness of hantaviruses in the region and assessment of symptomatic persons without known risk factors for infection. PMID:22709722

Environmental Variables Associated with Hantavirus Reservoirs and Other Small Rodent Species in Two National Parks in the Paraná Delta, Argentina: Implications for Disease Prevention.

PubMed

Vadell, María Victoria; Gómez Villafañe, Isabel Elisa

2016-06-01

Hantavirus pulmonary syndrome (HPS) is a severe zoonotic disease caused by hantaviruses hosted in various rodents species. In Argentina, its transmission to humans has been associated to exposure during activities such as farming, recreation, and tourism which are carried out in wild and rural areas. The aim of this study was to analyze the macro- and micro-habitat use and spatio-temporal variation of small sylvan rodents in Pre Delta and Islas de Santa Fe national parks, located in an HPS-endemic area of Argentina. Rodent communities were studied at six sites: two islands, a riparian forest, an inland forest, a marsh, and the margins of a pond. A total of 453 individuals of five species were captured with a trapping effort of 9471 trap-nights. Maximum species richness was found at the marsh and the pond margin sites. Abundance of rodents was influenced by flooding events. Two hantavirus reservoirs, Oligoryzomys flavescens and Akodon azarae, were identified in the area. O. flavescens was captured in every habitat, but it was dominant in Islas de Santa Fe National Park where its abundance was strongly influenced by flooding. A. azarae was captured in every habitat except on the islands. A. azarae behaved as a generalist species at a micro-habitat scale in every habitat of Pre Delta National Park except for the marsh where it selected patches with low vegetation height. Based on these results, several disease prevention measures, including the use of rodent-proof containers for food, and keeping the grass short in the camp site, are proposed in order to reduce the risk to visitors and residents of contracting HPS.

Recent Evidence of Hantavirus Circulation in the American Tropic

PubMed Central

Montoya-Ruiz, Carolina; Diaz, Francisco J.; Rodas, Juan D.

2014-01-01

Hantaan virus was discovered in Korea during the 1970s while other similar viruses were later reported in Asia and Europe. There was no information about hantavirus human infection in the Americas until 1993 when an outbreak was described in the United States. This event promoted new studies to find hantaviruses in the Americas. At first, many studies were conducted in Brazil, Argentina, Chile, Uruguay and Paraguay, while other Latin American countries began to report the presence of these agents towards the end of the 20th century. More than 30 hantaviruses have been reported in the Western Hemisphere with more frequent cases registered in the southern cone (Argentina, Chile, Uruguay, Paraguay, Bolivia and Brazil). However there was an important outbreak in 2000 in Panama and some rare events have been described in Peru, Venezuela and French Guiana. Since hantaviruses have only recently emerged as a potential threat in the tropical zones of the Americas, this review compiles recent hantavirus reports in Central America, the Caribbean islands and the northern region of South America. These studies have generated the discovery of new hantaviruses and could help to anticipate the presentation of possible future outbreaks in the region. PMID:24638203

Recent evidence of hantavirus circulation in the American tropic.

PubMed

Montoya-Ruiz, Carolina; Diaz, Francisco J; Rodas, Juan D

2014-03-14

Hantaan virus was discovered in Korea during the 1970s while other similar viruses were later reported in Asia and Europe. There was no information about hantavirus human infection in the Americas until 1993 when an outbreak was described in the United States. This event promoted new studies to find hantaviruses in the Americas. At first, many studies were conducted in Brazil, Argentina, Chile, Uruguay and Paraguay, while other Latin American countries began to report the presence of these agents towards the end of the 20th century. More than 30 hantaviruses have been reported in the Western Hemisphere with more frequent cases registered in the southern cone (Argentina, Chile, Uruguay, Paraguay, Bolivia and Brazil). However there was an important outbreak in 2000 in Panama and some rare events have been described in Peru, Venezuela and French Guiana. Since hantaviruses have only recently emerged as a potential threat in the tropical zones of the Americas, this review compiles recent hantavirus reports in Central America, the Caribbean islands and the northern region of South America. These studies have generated the discovery of new hantaviruses and could help to anticipate the presentation of possible future outbreaks in the region.

Knowledge, attitudes, and practices regarding hantavirus disease and acceptance of a vaccine trial in rural communities of southern Chile

PubMed Central

Valdivieso, Francisca; Gonzalez, Claudia; Najera, Manuel; Olea, Andrea; Cuiza, Analia; Aguilera, Ximena; Mertz, Gregory

2017-01-01

ABSTRACT Andes hantavirus cardiopulmonary syndrome, transmitted by Oligoryzomys longicaudatus, has no approved treatment, a case fatality rate of 35%, and documented person-to-person transmission. An Andes vaccine, highly needed for prevention, is in development. We aimed to evaluate knowledge, attitudes and practices (KAP) regarding hantavirus disease and willingness to participate in a future Andes vaccine trials through a cross sectional face-to-face oral survey of a randomly selected adult sample from 2 rural communes in southern Chile. Human subjects approval was obtained from our institutional IRBs, and participants signed informed consent. We enrolled 319 subjects from Corral and 321 from Curarrehue; 98% had heard about hantavirus disease and its reservoir but only half knew about transmission, symptoms and prevention. Participants fear the disease but are only partially aware of their own risk. One third of participants reported presence of rodents inside their homes. Despite moderate confidence in their health system, most subjects perceived vaccines as beneficial, and 93% would accept an approved hantavirus vaccine. Half would agree to participate in a vaccine trial and 29% would allow their children to participate. Motivations to participate were mainly altruistic, while risk perception was the main reason for declining. Knowledge about hantavirus disease and prevention practices require reinforcement, and a vaccine trial seems feasible in these populations. PMID:27830976

The pulmonary histopathology of anti-KS transfer RNA synthetase syndrome.

PubMed

Schneider, Frank; Aggarwal, Rohit; Bi, David; Gibson, Kevin; Oddis, Chester; Yousem, Samuel A

2015-01-01

The clinical spectrum of the antisynthetase syndromes (AS) has been poorly defined, although some frequently present with pulmonary manifestations. The anti-KS anti-asparaginyl-transfer RNA synthetase syndrome is one in which pulmonary interstitial lung disease is almost always present and yet the histopathologic spectrum is not well described. To define the morphologic manifestations of pulmonary disease in those patients with anti-KS antiasparaginyl syndrome. We reviewed the connective tissue disorder registry of the University of Pittsburgh and identified those patients with anti-KS autoantibodies who presented with interstitial lung disease and had surgical lung biopsies. The 5 patients with anti-KS antisynthetase syndrome were usually women presenting with dyspnea and without myositis, but with mechanic's hands (60%) and Raynaud phenomenon (40%). They most often presented with a usual interstitial pneumonia pattern of fibrosis (80%), with the final patient displaying organizing pneumonia. Pulmonary interstitial lung disease is a common presentation in patients with the anti-KS-antisynthetase syndrome, who are often women with rather subtle or subclinical connective tissue disease, whereas the literature emphasizes the nonspecific interstitial pneumonia pattern often diagnosed clinically. Usual interstitial pneumonia and organizing pneumonia patterns of interstitial injury need to be added to this clinical differential diagnosis.

Treatment of Hantavirus Pulmonary Syndrome

DTIC Science & Technology

2007-10-14

of Infectious Diseases, Ft. Detrick, MD, United States c Department of Internal Medicine, University of New Mexico , Albuquerque, NM, United States...Within ours the patient required mechanical ventilation and extracorporeal membrane xygenation (ECMO). Courtesy G. Mertz, University of New Mexico . hea...femoral artery and vein. The bed is versity of New Mexico . . Antiviral therapy Ribavirin was tested for efficacy in HFRS patients in China nd shown to

Preventing Hantavirus Pulmonary Syndrome (HPS)

MedlinePlus

... into contact with them. Seal up holes and gaps in your home or garage. Place traps in and around your home to decrease rodent infestation. Clean up any easy-to-get food. Recent research results show that many people who became ill ...

Phylogeny and origins of hantaviruses harbored by bats, insectivores, and rodents.

PubMed

Guo, Wen-Ping; Lin, Xian-Dan; Wang, Wen; Tian, Jun-Hua; Cong, Mei-Li; Zhang, Hai-Lin; Wang, Miao-Ruo; Zhou, Run-Hong; Wang, Jian-Bo; Li, Ming-Hui; Xu, Jianguo; Holmes, Edward C; Zhang, Yong-Zhen

2013-02-01

Hantaviruses are among the most important zoonotic pathogens of humans and the subject of heightened global attention. Despite the importance of hantaviruses for public health, there is no consensus on their evolutionary history and especially the frequency of virus-host co-divergence versus cross-species virus transmission. Documenting the extent of hantavirus biodiversity, and particularly their range of mammalian hosts, is critical to resolving this issue. Here, we describe four novel hantaviruses (Huangpi virus, Lianghe virus, Longquan virus, and Yakeshi virus) sampled from bats and shrews in China, and which are distinct from other known hantaviruses. Huangpi virus was found in Pipistrellus abramus, Lianghe virus in Anourosorex squamipes, Longquan virus in Rhinolophus affinis, Rhinolophus sinicus, and Rhinolophus monoceros, and Yakeshi virus in Sorex isodon, respectively. A phylogenetic analysis of the available diversity of hantaviruses reveals the existence of four phylogroups that infect a range of mammalian hosts, as well as the occurrence of ancient reassortment events between the phylogroups. Notably, the phylogenetic histories of the viruses are not always congruent with those of their hosts, suggesting that cross-species transmission has played a major role during hantavirus evolution and at all taxonomic levels, although we also noted some evidence for virus-host co-divergence. Our phylogenetic analysis also suggests that hantaviruses might have first appeared in Chiroptera (bats) or Soricomorpha (moles and shrews), before emerging in rodent species. Overall, these data indicate that bats are likely to be important natural reservoir hosts of hantaviruses.

Epidemiology of hantavirus infection in Thousand Islands regency of Jakarta, Indonesia.

PubMed

Ibrahim, Ima-Nurisa; Shimizu, Kenta; Yoshimatsu, Kumiko; Yunianto, Andre; Salwati, Ervi; Yasuda, Shumpei P; Koma, Takaaki; Endo, Rika; Arikawa, Jiro

2013-01-01

Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne zoonotic disease caused by hantavirus infection. Many HFRS cases have been reported in East Asia and North Europe, while the situation in Southeast Asia remains unclear. In this study, the prevalence of hantavirus infection in rodents and humans in Thousand Islands regency, which is close to the port of Jakarta, one of the largest historic ports in Indonesia, was investigated. A total of 170 rodents were captured in 2005, and 27 (15.9%) of the rodents were antibody-positive against Hantaan virus antigen in an immunofluorescence assay (IFA) and Western blotting. Despite the high prevalence in rodents, human sera collected from 31 patients with fever of unknown origin and 20 healthy volunteers in the islands in 2009 did not show positive reaction to the antigen in IFA. To identify the virus in rodents genetically, a total of 59 rodents were captured in 2009. Sera from the rodents were screened for antibody by ELISA, and lung tissues were subjected to RT-PCR. 20 (33.9%) of the 59 rodents were antibody-positive, and 3 of those 20 rodents were positive for S and M genome segments of hantaviruses. Genetic analysis showed that the viruses belonged to Seoul virus and formed a cluster with those in Vietnam and Singapore. These results suggest that a unique group of Seoul viruses has spread widely in Southeast Asia.

[Comprehensive characteristics of the pulmonary syndrome in chronic liver diseases].

PubMed

Pashchenko, I G; Romanov, A A; Zhumanbaeva, R M; Osmolovskiĭ, V S; Faliushina, N V

1988-01-01

Combined investigations have shown that the pulmonary syndrome in chronic liver diseases is a group of changes (heterogeneous in their structure and origin), most of which are of intercurrent nature (chronic bronchitis and its complications, chronic pneumonia), the lesser part of them is related directly to an inflammatory liver process and constitutes the true pulmonary syndrome (interstitial pneumonitis, fibrosing alveolitis). In view of the fact that chronic liver pathology is attended by concomitant disorders of pulmonary ventilation, hemodynamics and immunologic homestasis, the authors propose that they should be regarded as a risk factor contributing to the development of respiratory diseases.

Resolution of Behçet's syndrome associated pulmonary arterial aneurysms with infliximab.

PubMed

Schreiber, Benjamin E; Noor, Nadim; Juli, Christoph F; Haskard, Dorian O

2011-12-01

We describe the successful treatment of pulmonary arterial aneurysms in Behçet's syndrome using a tumor necrosis factor (TNF) inhibitor. A case is reported of Behçet's syndrome complicated by pulmonary arterial aneurysms that responded to anti-TNF therapy. This is accompanied by a literature review of previously published cases. We searched the English language medical literature using the PubMed and Medline search terms: "Behçet's," "Pulmonary aneurysms," and "infliximab," "etanercept," or "adalimumab." A 43-year-old man with a 6-month history of oral and genital ulcers, weight loss, and fatigue developed arterial aneurysms in the common carotid and common iliac arteries and thromboses in a femoral vein and pulmonary arteries. Treatment with high-dose oral corticosteroids and pulsed intravenous cyclophosphamide was initiated but while on treatment he developed pulmonary arterial aneurysms with hemoptysis. His treatment was changed to intravenous infliximab with methotrexate to which he showed a good response with marked clinical improvement, reduction in his inflammatory markers, and regression of the pulmonary arterial aneurysms. The review of the literature identified 3 reported cases of treatment of pulmonary arterial aneurysms in Behçet's syndrome with anti-TNF therapy, with good outcomes in each case. Pulmonary artery aneurysms are important complications of Behçet's syndrome. Anti-TNF inhibitors should be considered in patients who do not respond to treatment with corticosteroids and cyclophosphamide. Copyright © 2011 Elsevier Inc. All rights reserved.

A hantavirus pulmonary syndrome (HPS) DNA vaccine delivered using a spring-powered jet injector elicits a potent neutralizing antibody response in rabbits and nonhuman primates.

PubMed

Kwilas, Steve; Kishimori, Jennifer M; Josleyn, Matthew; Jerke, Kurt; Ballantyne, John; Royals, Michael; Hooper, Jay W

2014-01-01

Sin Nombre virus (SNV) and Andes virus (ANDV) cause most of the hantavirus pulmonary syndrome (HPS) cases in North and South America, respectively. The chances of a patient surviving HPS are only two in three. Previously, we demonstrated that SNV and ANDV DNA vaccines encoding the virus envelope glycoproteins elicit high-titer neutralizing antibodies in laboratory animals, and (for ANDV) in nonhuman primates (NHPs). In those studies, the vaccines were delivered by gene gun or muscle electroporation. Here, we tested whether a combined SNV/ANDV DNA vaccine (HPS DNA vaccine) could be delivered effectively using a disposable syringe jet injection (DSJI) system (PharmaJet, Inc). PharmaJet intramuscular (IM) and intradermal (ID) needle-free devices are FDA 510(k)-cleared, simple to use, and do not require electricity or pressurized gas. First, we tested the SNV DNA vaccine delivered by PharmaJet IM or ID devices in rabbits and NHPs. Both IM and ID devices produced high-titer anti-SNV neutralizing antibody responses in rabbits and NHPs. However, the ID device required at least two vaccinations in NHP to detect neutralizing antibodies in most animals, whereas all animals vaccinated once with the IM device seroconverted. Because the IM device was more effective in NHP, the Stratis(®) (PharmaJet IM device) was selected for follow-up studies. We evaluated the HPS DNA vaccine delivered using Stratis(®) and found that it produced high-titer anti-SNV and anti-ANDV neutralizing antibodies in rabbits (n=8/group) as measured by a classic plaque reduction neutralization test and a new pseudovirion neutralization assay. We were interested in determining if the differences between DSJI delivery (e.g., high-velocity liquid penetration through tissue) and other methods of vaccine injection, such as needle/syringe, might result in a more immunogenic DNA vaccine. To accomplish this, we compared the HPS DNA vaccine delivered by DSJI versus needle/syringe in NHPs (n=8/group). We found

Acute-onset chronic inflammatory demyelinating polyneuropathy in hantavirus and hepatitis B virus coinfection: A case report.

PubMed

Lim, Jong Youb; Lim, Young-Ho; Choi, Eun-Hi

2016-12-01

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired autoimmune disorder with progressive weakness. Acute-onset CIDP resembles Guillain-Barre syndrome (GBS), a rapidly progressive disorder, and follows a chronic course. To our knowledge, no case of acute-onset CIDP in hantavirus and hepatitis B virus (HBV) coinfection has been reported previously. We report a case of acute-onset CIDP that was initially diagnosed as GBS. A 44-year-old male logger complained of acute quadriplegia and dyspnea. Mechanical ventilation was initiated. He was an HBV carrier with mild elevation of hepatic enzyme, and positive for hantavirus antibody. He was diagnosed with GBS and immunoglobulin therapy was administered. After 8 months, quadriplegia and hypesthesia recurred. Immunoglobulin therapy at this time had no effect, but steroid therapy had some effect. A diagnosis of CIDP was made. After 2 months, severe extremity pain and dyspnea developed again, and steroid pulse therapy was initiated. Besides GBS, acute-onset CIDP can occur with hantavirus and HBV coinfection. Patients with this coinfection in whom GBS has been initially diagnosed should be followed up for a long time, because of the possibility of relapse or deterioration, and acute-onset CIDP should always be considered.

β2 integrin mediates hantavirus-induced release of neutrophil extracellular traps

PubMed Central

Raftery, Martin J.; Lalwani, Pritesh; Krautkrӓmer, Ellen; Peters, Thorsten; Scharffetter-Kochanek, Karin; Krüger, Renate; Hofmann, Jörg; Seeger, Karl; Krüger, Detlev H.

2014-01-01

Rodent-borne hantaviruses are emerging human pathogens that cause severe human disease. The underlying mechanisms are not well understood, as hantaviruses replicate in endothelial and epithelial cells without causing any cytopathic effect. We demonstrate that hantaviruses strongly stimulated neutrophils to release neutrophil extracellular traps (NETs). Hantavirus infection induced high systemic levels of circulating NETs in patients and this systemic NET overflow was accompanied by production of autoantibodies to nuclear antigens. Analysis of the responsible mechanism using neutrophils from β2 null mice identified β2 integrin receptors as a master switch for NET induction. Further experiments suggested that β2 integrin receptors such as complement receptor 3 (CR3) and 4 (CR4) may act as novel hantavirus entry receptors. Using adenoviruses, we confirmed that viral interaction with β2 integrin induced strong NET formation. Collectively, β2 integrin–mediated systemic NET overflow is a novel viral mechanism of immunopathology that may be responsible for characteristic aspects of hantavirus-associated disease such as kidney and lung damage. PMID:24889201

Effects of Humidity Variation on the Hantavirus Infection and Hemorrhagic Fever with Renal Syndrome Occurrence in Subtropical China

PubMed Central

Xiao, Hong; Huang, Ru; Gao, Li-Dong; Huang, Cun-Rui; Lin, Xiao-Ling; Li, Na; Liu, Hai-Ning; Tong, Shi-Lu; Tian, Huai-Yu

2016-01-01

Infection rates of rodents have a significant influence on the transmission of hemorrhagic fever with renal syndrome (HFRS). In this study, four cities and two counties with high HFRS incidence in eastern Hunan Province in China were studied, and surveillance data of rodents, as well as HFRS cases and related environmental variables from 2007 to 2010, were collected. Results indicate that the distribution and infection rates of rodents are closely associated with environmental conditions. Hantavirus infections in rodents were positively correlated with temperature vegetation dryness index and negatively correlated with elevation. The predictive risk maps based on multivariate regression model revealed that the annual variation of infection risks is small, whereas monthly variation is large and corresponded well to the seasonal variation of human HFRS incidence. The identification of risk factors and risk prediction provides decision support for rodent surveillance and the prevention and control of HFRS. PMID:26711521

The association between the metabolic syndrome and metabolic syndrome score and pulmonary function in non-smoking adults.

PubMed

Yoon, Hyun; Gi, Mi Young; Cha, Ju Ae; Yoo, Chan Uk; Park, Sang Muk

2018-03-01

This study assessed the association of metabolic syndrome and metabolic syndrome score with the predicted forced vital capacity and predicted forced expiratory volume in 1 s (predicted forced expiratory volume in 1 s) values in Korean non-smoking adults. We analysed data obtained from 6684 adults during the 2013-2015 Korean National Health and Nutrition Examination Survey. After adjustment for related variables, metabolic syndrome ( p < 0.001) and metabolic syndrome score ( p < 0.001) were found to be inversely associated with the predicted forced vital capacity and forced expiratory volume in 1 s values. The odds ratios of restrictive pulmonary disease (the predicted forced vital capacity < 80.0% with forced expiratory volume in 1 s/FVC ⩾ 70.0%) by metabolic syndrome score with metabolic syndrome score 0 as a reference group showed no significance for metabolic syndrome score 1 [1.061 (95% confidence interval, 0.755-1.490)] and metabolic syndrome score 2 [1.247 (95% confidence interval, 0.890-1.747)], but showed significant for metabolic syndrome score 3 [1.433 (95% confidence interval, 1.010-2.033)] and metabolic syndrome score ⩾ 4 [1.760 (95% confidence interval, 1.216-2.550)]. In addition, the odds ratio of restrictive pulmonary disease of the metabolic syndrome [1.360 (95% confidence interval, 1.118-1.655)] was significantly higher than those of non-metabolic syndrome. Metabolic syndrome and metabolic syndrome score were inversely associated with the predicted forced vital capacity and forced expiratory volume in 1 s values in Korean non-smoking adults. In addition, metabolic syndrome and metabolic syndrome score were positively associated with the restrictive pulmonary disease.

Fused pulmonary lobes is a rat model of human Fraser syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kiyozumi, Daiji; Nakano, Itsuko; Takahashi, Ken L.

Highlights: {yields} Fused pulmonary lobes (fpl) mutant rats exhibit similar phenotypes to Fraser syndrome. {yields} The fpl gene harbors a nonsense mutation in Fraser syndrome-associated gene Frem2. {yields} Fpl mutant is defined as a first model of human Fraser syndrome in rats. -- Abstract: Fused pulmonary lobes (fpl) is a mutant gene that is inherited in an autosomal recessive manner and causes various developmental defects, including fusion of pulmonary lobes, and eyelid and digit anomalies in rats. Since these developmental defects closely resemble those observed in patients with Fraser syndrome, a recessive multiorgan disorder, and its model animals, we investigatedmore » whether the abnormal phenotypes observed in fpl/fpl mutant rats are attributable to a genetic disorder similar to Fraser syndrome. At the epidermal basement membrane in fpl/fpl mutant neonates, the expression of QBRICK, a basement membrane protein whose expression is attenuated in Fraser syndrome model mice, was greatly diminished compared with control littermates. Quantitative RT-PCR analyses of Fraser syndrome-related genes revealed that Frem2 transcripts were markedly diminished in QBRICK-negative embryos. Genomic DNA sequencing of the fpl/fpl mutant identified a nonsense mutation that introduced a stop codon at serine 2005 in Frem2. These findings indicate that the fpl mutant is a rat model of human Fraser syndrome.« less

Novel Hantavirus in the Flat-Skulled Shrew (Sorex roboratus)

PubMed Central

Kang, Hae Ji; Arai, Satoru; Hope, Andrew G.; Cook, Joseph A.

2010-01-01

Abstract Genetically distinct hantaviruses have been identified recently in multiple species of shrews (Order Soricomorpha, Family Soricidae) in Eurasia and North America. To corroborate decades-old reports of hantaviral antigens in shrews from Russia, archival liver and lung tissues from 4 Siberian large-toothed shrews (Sorex daphaenodon), 5 Eurasian least shrews (Sorex minutissimus), 12 flat-skulled shrews (Sorex roboratus), and 18 tundra shrews (Sorex tundrensis), captured in the Sakha Republic in northeastern Siberia during July and August 2006, were analyzed for hantavirus RNA by reverse transcription–polymerase chain reaction. A novel hantavirus, named Kenkeme virus, was detected in a flat-skulled shrew. Sequence analysis of the full-length S and partial M and L segments indicated that Kenkeme virus was genetically and phylogenetically distinct from Seewis virus harbored by the Eurasian common shrew (Sorex araneus), as well as all other rodent-, soricid-, and talpid-borne hantaviruses. PMID:20426682

Estimation of main diversification time-points of hantaviruses using phylogenetic analyses of complete genomes.

PubMed

Castel, Guillaume; Tordo, Noël; Plyusnin, Alexander

2017-04-02

Because of the great variability of their reservoir hosts, hantaviruses are excellent models to evaluate the dynamics of virus-host co-evolution. Intriguing questions remain about the timescale of the diversification events that influenced this evolution. In this paper we attempted to estimate the first ever timing of hantavirus diversification based on thirty five available complete genomes representing five major groups of hantaviruses and the assumption of co-speciation of hantaviruses with their respective mammal hosts. Phylogenetic analyses were used to estimate the main diversification points during hantavirus evolution in mammals while host diversification was mostly estimated from independent calibrators taken from fossil records. Our results support an earlier developed hypothesis of co-speciation of known hantaviruses with their respective mammal hosts and hence a common ancestor for all hantaviruses carried by placental mammals. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular characterization of two hantavirus strains from different rattus species in Singapore

PubMed Central

2010-01-01

Background Hantaviruses cause human disease in endemic regions around the world. Outbreaks of hantaviral diseases have been associated with changes in rodent population density and adaptation to human settlements leading to their proliferation in close proximity to human dwellings. In a parallel study initiated to determine the prevalence of pathogens in Singapore's wild rodent population, 1206 rodents were trapped and screened. The findings established a hantavirus seroprevalence of 34%. This paper describes the molecular characterization of hantaviruses from Rattus norvegicus and Rattus tanezumi, the predominant rodents caught in urban Singapore. Methodology Pan-hanta RT-PCR performed on samples of Rattus norvegicus and Rattus tanezumi indicated that 27 (2.24%) of the animals were positive. sequence analysis of the S and M segments established that two different hantavirus strains circulate in the rodent population of Singapore. Notably, the hantavirus strains found in Rattus norvegicus clusters with other Asian Seoul virus sequences, while the virus strains found in Rattus tanezumi had the highest sequence similarity to the Serang virus from Rattus tanezumi in Indonesia, followed by Cambodian hantavirus isolates and the Thailand virus isolated from Bandicota indica. Conclusions Sequence analysis of the S and M segments of hantavirus strains found in Rattus norvegicus (Seoul virus strain Singapore) and Rattus tanezumi (Serang virus strain Jurong TJK/06) revealed that two genetically different hantavirus strains were found in rodents of Singapore. Evidently, together with Serang, Cambodian and Thailand virus the Jurong virus forms a distinct phylogroup. Interestingly, these highly similar virus strains have been identified in different rodent hosts. Further studies are underway to analyze the public health significance of finding hantavirus strains in Singapore rodents. PMID:20096099

Global Diversity and Distribution of Hantaviruses and Their Hosts.

PubMed

Milholland, Matthew T; Castro-Arellano, Iván; Suzán, Gerardo; Garcia-Peña, Gabriel E; Lee, Thomas E; Rohde, Rodney E; Alonso Aguirre, A; Mills, James N

2018-04-30

Rodents represent 42% of the world's mammalian biodiversity encompassing 2,277 species populating every continent (except Antarctica) and are reservoir hosts for a wide diversity of disease agents. Thus, knowing the identity, diversity, host-pathogen relationships, and geographic distribution of rodent-borne zoonotic pathogens, is essential for predicting and mitigating zoonotic disease outbreaks. Hantaviruses are hosted by numerous rodent reservoirs. However, the diversity of rodents harboring hantaviruses is likely unknown because research is biased toward specific reservoir hosts and viruses. An up-to-date, systematic review covering all known rodent hosts is lacking. Herein, we document gaps in our knowledge of the diversity and distribution of rodent species that host hantaviruses. Of the currently recognized 681 cricetid, 730 murid, 61 nesomyid, and 278 sciurid species, we determined that 11.3, 2.1, 1.6, and 1.1%, respectively, have known associations with hantaviruses. The diversity of hantaviruses hosted by rodents and their distribution among host species supports a reassessment of the paradigm that each virus is associated with a single-host species. We examine these host-virus associations on a global taxonomic and geographical scale with emphasis on the rodent host diversity and distribution. Previous reviews have been centered on the viruses and not the mammalian hosts. Thus, we provide a perspective not previously addressed.

Anthropogenic habitat disturbance and the dynamics of hantavirus using remote sensing, GIS, and a spatially explicit agent-based model

NASA Astrophysics Data System (ADS)

Cao, Lina

Sin Nombre virus (SNV), a strain of hantavirus, causes hantavirus pulmonary syndrome (HPS) in humans, a deadly disease with high mortality rate (>50%). The primary virus host is deer mice, and greater deer mice abundance has been shown to increase the human risk of HPS. There is a great need in understanding the nature of the virus host, its temporal and spatial dynamics, and its relation to the human population with the purpose of predicting human risk of the disease. This research studies SNV dynamics in deer mice in the Great Basin Desert of central Utah, USA using multiyear field data and integrated geospatial approaches including remote sensing, Geographic Information System (GIS), and a spatially explicit agent-based model. The goal is to advance our understanding of the important ecological and demographic factors that affect the dynamics of deer mouse population and SNV prevalence. The primary research question is how climate, habitat disturbance, and deer mouse demographics affect deer mouse population density, its movement, and SNV prevalence in the sagebrush habitat. The results show that the normalized difference vegetation index (NDVI) and the enhanced vegetation index (EVI) can be good predictors of deer mouse density and the number of infected deer mice with a time lag of 1.0 to 1.3 years. This information can be very useful in predicting mouse abundance and SNV risk. The results also showed that climate, mouse density, sex, mass, and SNV infection had significant effects on deer mouse movement. The effect of habitat disturbance on mouse movement varies according to climate conditions with positive relationship in predrought condition and negative association in postdrought condition. The heavier infected deer mice moved the most. Season and disturbance alone had no significant effects. The spatial agent-based model (SABM) simulation results show that prevalence was negatively related to the disturbance levels and the sensitivity analysis showed that

Preliminary selection and evaluation of the binding of aptamers against a Hantavirus antigen using fluorescence spectroscopy and modeling

NASA Astrophysics Data System (ADS)

Missailidis, Sotiris; de Oliveira, Renata Carvalho; Silva, Dilson; Cortez, Célia Martins; Guterres, Alexandro; Vicente, Luciana Helena Bassan; de Godoy, Daniela Tupy; Lemos, Elba

2015-12-01

In this study we have aimed to develop novel aptamers against the Hantavirus nucleoprotein N, a valid antigen already used in the Hantavirus reference laboratory of the Institute Oswaldo Cruz in Rio de Janeiro, Brazil. Such aptamers, if they are found to bind with high affinity and specificity for the selected hantavirus antigen, they could be translated into novel diagnostic assays with the ability to provide early detection for hantaviroses and their related disease syndromes. In a preliminary screening, we have managed to identify three aptamer species. We have analyzed a short and a long version of these aptamer using fluorescence spectroscopy and modelled their binding. We have identified Stern-Volmer constants for the selected aptamers, which have shown affinity for their target, with a different binding between the short and the long versions of them. Short aptamers have shown to have a higher Stern-Volmer constant and the ability to potentially bind to more than one binding site on the antigen. The information provided by the spectroscopic screening has been invaluable in allowing us to define candidates for further development into diagnostic assays.

Evolutionary Insights from a Genetically Divergent Hantavirus Harbored by the European Common Mole (Talpa europaea)

PubMed Central

Kang, Hae Ji; Bennett, Shannon N.; Sumibcay, Laarni; Arai, Satoru; Hope, Andrew G.; Mocz, Gabor; Song, Jin-Won; Cook, Joseph A.; Yanagihara, Richard

2009-01-01

Background The discovery of genetically distinct hantaviruses in shrews (Order Soricomorpha, Family Soricidae) from widely separated geographic regions challenges the hypothesis that rodents (Order Rodentia, Family Muridae and Cricetidae) are the primordial reservoir hosts of hantaviruses and also predicts that other soricomorphs harbor hantaviruses. Recently, novel hantavirus genomes have been detected in moles of the Family Talpidae, including the Japanese shrew mole (Urotrichus talpoides) and American shrew mole (Neurotrichus gibbsii). We present new insights into the evolutionary history of hantaviruses gained from a highly divergent hantavirus, designated Nova virus (NVAV), identified in the European common mole (Talpa europaea) captured in Hungary. Methodology/Principal Findings Pair-wise alignment and comparison of the full-length S- and L-genomic segments indicated moderately low sequence similarity of 54–65% and 46–63% at the nucleotide and amino acid levels, respectively, between NVAV and representative rodent- and soricid-borne hantaviruses. Despite the high degree of sequence divergence, the predicted secondary structure of the NVAV nucleocapsid protein exhibited the characteristic coiled-coil domains at the amino-terminal end, and the L-segment motifs, typically found in hantaviruses, were well conserved. Phylogenetic analyses, using maximum-likelihood and Bayesian methods, showed that NVAV formed a distinct clade that was evolutionarily distant from all other hantaviruses. Conclusions Newly identified hantaviruses harbored by shrews and moles support long-standing virus-host relationships and suggest that ancestral soricomorphs, rather than rodents, may have been the early or original mammalian hosts. PMID:19582155

A non-randomized multicentre trial of human immune plasma for treatment of hantavirus cardiopulmonary syndrome caused by Andes virus.

PubMed

Vial, Pablo A; Valdivieso, Francisca; Calvo, Mario; Rioseco, M Luisa; Riquelme, Raul; Araneda, Andres; Tomicic, Vinko; Graf, Jerónimo; Paredes, Laura; Florenzano, Matias; Bidart, Teresa; Cuiza, Analia; Marco, Claudia; Hjelle, Brian; Ye, Chunyan; Hanfelt-Goade, Diane; Vial, Cecilia; Rivera, Juan C; Delgado, Iris; Mertz, Gregory J

2015-01-01

In Chile, Andes virus (ANDV) is the sole aetiological agent of hantavirus cardiopulmonary syndrome (HCPS) with mean annual incidence of 55 cases, 32% case fatality rate (CFR) and no specific treatment. Neutralizing antibody (NAb) titres at hospital admission correlate inversely with HCPS severity. We designed an open trial to explore safety and efficacy and evaluate pharmacokinetics of immune plasma as a treatment strategy for this disease. We performed plasmapheresis on donors at least 6 months after HCPS and measured NAb titres through a focus-reduction neutralization test. Subjects admitted to 10 study sites with suspected/confirmed HCPS were eligible for treatment with immune plasma by intravenous infusion at an ANDV NAb dose of 5,000 U/kg. HCPS was confirmed through immunoglobulin M serology or reverse transcriptase-PCR. The main outcome was mortality within 30 days. From 2008-2012, we enrolled and treated 32 cases and confirmed HCPS in 29. CFR of hantavirus plasma-treated cases was 4/29 (14%); CFR of non-treated cases in the same period in Chile was 63/199 (32%; P=0.049, OR=0.35, CI=0.12, 0.99); CFR of non-treated cases at the same study sites between 2005-2012 was 18/66 (27%; (P=0.15, OR=0.43, CI=0.14, 1.34) and CFR in a previous methylprednisolone treatment study was 20/60 (33%; P=0.052, OR=0.32, CI=0.10, 1.00). We detected no serious adverse events associated to plasma infusion. Plasma NAb titres reached in recipients were variable and viral load remained stable. Human ANDV immune plasma infusion appears safe for HCPS. We observed a decrease in CFR in treated cases with borderline significance that will require further studies for confirmation.

Hemorrhagic fever with renal syndrome caused by Hantaan virus infection in four pregnant Chinese women.

PubMed

Ji, Fanpu; Zhao, Wenxuan; Liu, Hailing; Zheng, Hongbo; Wang, Shengbang; He, Caini; Wang, Wenjun; Zhang, Ruijuan; Bai, Dan; Tian, Changyin; Zhao, Wenxue; Deng, Hong

2017-10-01

Hantavirus infection during pregnancy can influence both maternal and fetal outcomes. Here, we describe four cases of hemorrhagic fever with renal syndrome (HFRS) in pregnant Chinese women. The HFRS put these women at increased risk for severe illness, despite the patients' symptomologies in the onset phase were similar to those observed in non-pregnant HFRS patients, such as fever, headache, nausea, and thrombocytopenia. Pregnant women appeared to have a more severe status, presenting with severe complications, such as hypervolemia and pulmonary edema. Nevertheless, with appropriate management, mothers with HFRS may carry to full-term and breastfeeding maybe safe and feasible. © 2017 Wiley Periodicals, Inc.

Biological control agents elevate hantavirus by subsidizing deer mouse populations.

PubMed

Pearson, Dean E; Callaway, Ragan M

2006-04-01

Biological control of exotic invasive plants using exotic insects is practiced under the assumption that biological control agents are safe if they do not directly attack non-target species. We tested this assumption by evaluating the potential for two host-specific biological control agents (Urophora spp.), widely established in North America for spotted knapweed (Centaurea maculosa) control, to indirectly elevate Sin Nombre hantavirus by providing food subsidies to populations of deer mice (Peromyscus maniculatus), the primary reservoir for the virus. We show that seropositive deer mice (mice testing positive for hantavirus) were over three times more abundant in the presence of the biocontrol food subsidy. Elevating densities of seropositive mice may increase risk of hantavirus infection in humans and significantly alter hantavirus ecology. Host specificity alone does not ensure safe biological control. To minimize indirect risks to non-target species, biological control agents must suppress pest populations enough to reduce their own numbers.

Severe Cushing's syndrome and bilateral pulmonary nodules: beyond ectopic ACTH.

PubMed

Tavares Bello, Carlos; van der Poest Clement, Emma; Feelders, Richard

2017-01-01

Cushing's syndrome is a rare disease that results from prolonged exposure to supraphysiological levels of glucocorticoids. Severe and rapidly progressive cases are often, but not exclusively, attributable to ectopic ACTH secretion. Extreme hypercortisolism usually has florid metabolic consequences and is associated with an increased infectious and thrombotic risk. The authors report on a case of a 51-year-old male that presented with severe Cushing's syndrome secondary to an ACTH-secreting pituitary macroadenoma, whose diagnostic workup was affected by concurrent subclinical multifocal pulmonary infectious nodules. The case is noteworthy for the atypically severe presentation of Cushing's disease, and it should remind the clinician of the possible infectious and thrombotic complications associated with Cushing's syndrome. Severe Cushing's syndrome is not always caused by ectopic ACTH secretion.Hypercortisolism is a state of immunosuppression, being associated with an increased risk for opportunistic infections.Infectious pulmonary infiltrates may lead to imaging diagnostic dilemmas when investigating a suspected ectopic ACTH secretion.Cushing's syndrome carries an increased thromboembolic risk that may even persist after successful surgical management.Antibiotic and venous thromboembolism prophylaxis should be considered in every patient with severe Cushing's syndrome.

Hantavirus-induced disruption of the endothelial barrier: neutrophils are on the payroll.

PubMed

Schönrich, Günther; Krüger, Detlev H; Raftery, Martin J

2015-01-01

Viral hemorrhagic fever caused by hantaviruses is an emerging infectious disease for which suitable treatments are not available. In order to improve this situation a better understanding of hantaviral pathogenesis is urgently required. Hantaviruses infect endothelial cell layers in vitro without causing any cytopathogenic effect and without increasing permeability. This implies that the mechanisms underlying vascular hyperpermeability in hantavirus-associated disease are more complex and that immune mechanisms play an important role. In this review we highlight the latest developments in hantavirus-induced immunopathogenesis. A possible contribution of neutrophils has been neglected so far. For this reason, we place special emphasis on the pathogenic role of neutrophils in disrupting the endothelial barrier.

Pulmonary embolism after long duration rail travel: economy class syndrome or rail coach syndrome.

PubMed

Mittal, S K; Chopra, S; Calton, R

2011-07-01

Pulmonary embolism after long duration air travel is well described. However it can also occur following a long duration rail or road transport. We present a case of 43 year old male who developed deep venous thrombosis and acute pulmonary embolism after a long rail journey. We propose to call it as rail coach syndrome and stress the need for taking the same preventive measures as recommended for airline passengers.

The Association between Hantavirus Infection and Selenium Deficiency in Mainland China

PubMed Central

Fang, Li-Qun; Goeijenbier, Marco; Zuo, Shu-Qing; Wang, Li-Ping; Liang, Song; Klein, Sabra L.; Li, Xin-Lou; Liu, Kun; Liang, Lu; Gong, Peng; Glass, Gregory E.; van Gorp, Eric; Richardus, Jan H.; Ma, Jia-Qi; Cao, Wu-Chun; de Vlas, Sake J.

2015-01-01

Hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses and transmitted by rodents is a significant public health problem in China, and occurs more frequently in selenium-deficient regions. To study the role of selenium concentration in HFRS incidence we used a multidisciplinary approach combining ecological analysis with preliminary experimental data. The incidence of HFRS in humans was about six times higher in severe selenium-deficient and double in moderate deficient areas compared to non-deficient areas. This association became statistically stronger after correction for other significant environment-related factors (low elevation, few grasslands, or an abundance of forests) and was independent of geographical scale by separate analyses for different climate regions. A case-control study of HFRS patients admitted to the hospital revealed increased activity and plasma levels of selenium binding proteins while selenium supplementation in vitro decreased viral replication in an endothelial cell model after infection with a low multiplicity of infection (MOI). Viral replication with a higher MOI was not affected by selenium supplementation. Our findings indicate that selenium deficiency may contribute to an increased prevalence of hantavirus infections in both humans and rodents. Future studies are needed to further examine the exact mechanism behind this observation before selenium supplementation in deficient areas could be implemented for HFRS prevention. PMID:25609306

Spatial spread of the Hantavirus infection

NASA Astrophysics Data System (ADS)

Reinoso, José A.; de la Rubia, F. Javier

2015-03-01

The spatial propagation of Hantavirus-infected mice is considered a serious threat for public health. We analyze the spatial spread of the infected mice by including diffusion in the stage-dependent model for Hantavirus infection recently proposed by Reinoso and de la Rubia [Phys. Rev. E 87, 042706 (2013), 10.1103/PhysRevE.87.042706]. We consider a general scenario in which mice propagate in fronts from their refugia to the surroundings and find an expression for the speed of the front of infected mice. We also introduce a depletion time that measures the time scale for an appreciable impoverishment of the environment conditions and show how this new situation may change the spreading of the infection significantly.

Pulmonary hypertension due to acute respiratory distress syndrome

PubMed Central

Ñamendys-Silva, S.A.; Santos-Martínez, L.E.; Pulido, T.; Rivero-Sigarroa, E.; Baltazar-Torres, J.A.; Domínguez-Cherit, G.; Sandoval, J.

2014-01-01

Our aims were to describe the prevalence of pulmonary hypertension in patients with acute respiratory distress syndrome (ARDS), to characterize their hemodynamic cardiopulmonary profiles, and to correlate these parameters with outcome. All consecutive patients over 16 years of age who were in the intensive care unit with a diagnosis of ARDS and an in situ pulmonary artery catheter for hemodynamic monitoring were studied. Pulmonary hypertension was diagnosed when the mean pulmonary artery pressure was >25 mmHg at rest with a pulmonary artery occlusion pressure or left atrial pressure <15 mmHg. During the study period, 30 of 402 critically ill patients (7.46%) who were admitted to the ICU fulfilled the criteria for ARDS. Of the 30 patients with ARDS, 14 met the criteria for pulmonary hypertension, a prevalence of 46.6% (95% CI; 28-66%). The most common cause of ARDS was pneumonia (56.3%). The overall mortality was 36.6% and was similar in patients with and without pulmonary hypertension. Differences in patients' hemodynamic profiles were influenced by the presence of pulmonary hypertension. The levels of positive end-expiratory pressure and peak pressure were higher in patients with pulmonary hypertension, and the PaCO2 was higher in those who died. The level of airway pressure seemed to influence the onset of pulmonary hypertension. Survival was determined by the severity of organ failure at admission to the intensive care unit. PMID:25118626

Placebo-controlled, double-blind trial of intravenous ribavirin for the treatment of hantavirus cardiopulmonary syndrome in North America.

PubMed

Mertz, Gregory J; Miedzinski, Lil; Goade, Diane; Pavia, Andrew T; Hjelle, Brian; Hansbarger, Christine O; Levy, Howard; Koster, Frederick T; Baum, Kenneth; Lindemulder, Adeline; Wang, Wenquan; Riser, Laura; Fernandez, Humberto; Whitley, Richard J

2004-11-01

BACKGROUND. Ribavirin is active in vitro against hantaviruses, but the findings of an open trial of the use of intravenous ribavirin for the treatment of hantavirus cardiopulmonary syndrome (HCPS) were inconclusive. Subjects with suspected HCPS in the prodrome or cardiopulmonary phase but without shock were eligible for randomization to receive either intravenous ribavirin (33 mg/kg [

A hantavirus causing hemorrhagic fever with renal syndrome requires gC1qR/p32 for efficient cell binding and infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Yun; Kwon, Young-Chan; Kim, Soo-In

Hantaan virus (HTNV) is a pathogenic hantavirus that causes hemorrhagic fever with renal syndrome (HFRS). HTNV infection is mediated by {alpha}v{beta}3 integrin. We used protein blots of Vero E6 cell homogenates to demonstrate that radiolabeled HTNV virions bind to gC1qR/p32, the acidic 32-kDa protein known as the receptor for the globular head domain of complement C1q. RNAi-mediated suppression of gC1qR/p32 markedly reduced HTNV binding and infection in human lung epithelial A549 cells. Conversely, transient expression of either simian or human gC1qR/p32 rendered non-permissive CHO cells susceptible to HTNV infection. These results suggest an important role for gC1qR/p32 in HTNV infectionmore » and pathogenesis.« less

Changes in Diversification Patterns and Signatures of Selection during the Evolution of Murinae-Associated Hantaviruses

PubMed Central

Castel, Guillaume; Razzauti, Maria; Jousselin, Emmanuelle; Kergoat, Gael J.; Cosson, Jean-François

2014-01-01

In the last 50 years, hantaviruses have significantly affected public health worldwide, but the exact extent of the distribution of hantavirus diseases, species and lineages and the risk of their emergence into new geographic areas are still poorly known. In particular, the determinants of molecular evolution of hantaviruses circulating in different geographical areas or different host species are poorly documented. Yet, this understanding is essential for the establishment of more accurate scenarios of hantavirus emergence under different climatic and environmental constraints. In this study, we focused on Murinae-associated hantaviruses (mainly Seoul Dobrava and Hantaan virus) using sequences available in GenBank and conducted several complementary phylogenetic inferences. We sought for signatures of selection and changes in patterns and rates of diversification in order to characterize hantaviruses’ molecular evolution at different geographical scales (global and local). We then investigated whether these events were localized in particular geographic areas. Our phylogenetic analyses supported the assumption that RNA virus molecular variations were under strong evolutionary constraints and revealed changes in patterns of diversification during the evolutionary history of hantaviruses. These analyses provide new knowledge on the molecular evolution of hantaviruses at different scales of time and space. PMID:24618811

Unprovoked Pulmonary Embolism in a Young Patient with Marfan Syndrome.

PubMed

Pak, Stella; Kilgore, Andrew; Thornhill, Rosanne; Rako, Kyle; Meier, Ali; Pora, Gavriella; Costello, Jillian M; Dee, Christine

2017-09-05

Marfan syndrome is a rare connective tissue disorder with a prevalence of approximately 2 to 3 per 10,000 individuals. There have been some reports of young patients with Marfan syndrome developing arteriovenous thromboembolism. These events were unprovoked and recurrent. Owing to its rarity, hypercoagulopathy and other metabolic derangement in patients with Marfan syndrome remains largely unknown. Herein, we report a case of a young man with Marfan syndrome who had myocardial infarction and pulmonary embolism. We hope that this case adds to the scant body of knowledge about this patient population.

Tetralogy of Fallot with absent pulmonary valve syndrome; appropriate surgical strategies.

PubMed

Shahid, Fatima; Siddiqui, Maria Tariq; Amanullah, Muhammad Muneer

2015-05-01

To evaluate patients presenting with Tetralogy of Fallot with absent pulmonary valve syndrome to a tertiary care hospital and their surgical management. The retrospective study was conducted at Congenital Cardiac Services, Aga Khan University Hospital, Karachi, Pakistan, and comprised data of Tetralogy of Fallot patients between April 2007 and June 2012. Data was analysed together with follow-up echocardiography. Variables assessed included demographics, imaging, operative technique, complications, post-operative recovery and follow-up echocardiography. SPSS 17 was used for statistical analysis. Of the 204 patients, 6 (3%) had undergone surgical correction for Tetralogy of Fallot with absent pulmonary valve syndrome. All 6(100%) patients underwent complete repair. Median age for surgery was 8.5 years (range: 0.5-29 years). Of the different surgical strategies used, Contegra and Bioprosthetic valve placement had satisfactory outcome with minimal gradient at Right Ventricular Outflow Tract, good ventricular function and mild valvular regurgitation. One (16.6%) patient with Trans Annular Patch developed post-operative Right Ventricle Outflow Tract gradient of 80mmHg with moderate pulmonary regurgitation. One (16.6%) patient with monocusp valve developed free pulmonary regurgitation at 6 months. The other 4(66.6%) patients are currently free from any complications or re-intervention. Early surgery is preferred in symptomatic patients. The repair depends upon achieving integrity of pulmonary circulation which is best achieved by using right ventricle to pulmonary artery conduit or inserting a pulmonary valve.

Dobrava hantavirus variants found in Apodemus flavicollis mice in Kırklareli Province, Turkey.

PubMed

Polat, Ceylan; Sironen, Tarja; Plyusnina, Angelina; Karatas, Ahmet; Sozen, Mustafa; Matur, Ferhat; Vapalahti, Olli; Oktem, I Mehmet Ali; Plyusnin, Alexander

2018-05-01

Hantaviruses infect humans via inhalation of viral particles within secretions of infected rodents or rarely through direct contact with infected rodents. Determining the prevalence of hantavirus infections among rodent populations is of vital importance to obtain information on hantavirus-related cases and to predict possible outbreaks. We hypothesized that DOBV strains circulating in the Thrace Region in Turkey would be related to other Balkan DOBV strains. In this study, hantavirus infections in the rodent population of the Kırklareli-İğneada Region (north-western Turkey, near the Bulgarian border) were investigated. This region is of particular importance, as it is located in the south-eastern margin of the European continent and was used as an entrance point of Asian faunal elements into Europe. DOBV infection was detected in eight of 73 rodents; all were of the Apodemus flavicollis species. Partial sequences of the viral S-, M-, and L-genome segments were recovered and compared with previously reported DOBV sequences. The newly characterized Turkish strains were similar to other DOBV variants. Silent nucleotide mutations were dominant. The hantavirus prevalence in the İğneada region was similar to what has been reported in Greece and Bulgaria. For the first time, the M-segment sequences of DOBV from Turkey were recovered and genetic data of hantaviruses from Thrace region of Turkey were obtained. © 2018 Wiley Periodicals, Inc.

Partial anomalous pulmonary venous return in Turner syndrome.

PubMed

van den Hoven, Allard T; Chelu, Raluca G; Duijnhouwer, Anthonie L; Demulier, Laurent; Devos, Daniel; Nieman, Koen; Witsenburg, Maarten; van den Bosch, Annemien E; Loeys, Bart L; van Hagen, Iris M; Roos-Hesselink, Jolien W

2017-10-01

The aim of this study is to describe the prevalence, anatomy, associations and clinical impact of partial anomalous pulmonary venous return in patients with Turner syndrome. All Turner patients who presented at our Turner clinic, between January 2007 and October 2015 were included in this study and underwent ECG, echocardiography and advanced imaging such as cardiac magnetic resonance or computed tomography as part of their regular clinical workup. All imaging was re-evaluated and detailed anatomy was described. Partial anomalous pulmonary venous return was diagnosed in 24 (25%) out of 96 Turner patients included and 14 (58%) of these 24 partial anomalous pulmonary venous return had not been reported previously. Right atrial or ventricular dilatation was present in 11 (46%) of 24 partial anomalous pulmonary venous return patients. When studied with advanced imaging modalities and looked for with specific attention, PAPVR is found in 1 out of 4 Turner patients. Half of these patients had right atrial and/or ventricular dilatation. Evaluation of pulmonary venous return should be included in the standard protocol in all Turner patients. Copyright © 2017. Published by Elsevier B.V.

Climate Variability and the Occurrence of Human Puumala Hantavirus Infections in Europe: A Systematic Review.

PubMed

Roda Gracia, J; Schumann, B; Seidler, A

2015-09-01

Hantaviruses are distributed worldwide and are transmitted by rodents. In Europe, the infection usually manifests as a mild form of haemorrhagic fever with renal syndrome (HFRS) known as nephropathia epidemica (NE), which is triggered by the virus species Puumala. Its host is the bank vole (Myodes glareolus). In the context of climate change, interest in the role of climatic factors for the disease has increased. A systematic review was conducted to investigate the association between climate variability and the occurrence of human Puumala hantavirus infections in Europe. We performed a literature search in the databases MEDLINE, EMBASE and Web of Science. Studies that investigated Puumala virus infection and climatic factors in any European country with a minimum collection period of 2 years were included. The selection of abstracts and the evaluation of included studies were performed by two independent reviewers. A total of 434 titles were identified in the databases, of which nine studies fulfilled the inclusion criteria. The majority of studies were conducted in central Europe (Belgium, France and Germany), while only two came from the north (Sweden) and one from the south (Bosnia). Strong evidence was found for a positive association between temperature and NE incidence in central Europe, while the evidence for northern Europe so far appears insufficient. Results regarding precipitation were contradictory. Overall, the complex relationships between climate and hantavirus infections need further exploration to identify specific health risks and initiate appropriate intervention measures in the context of climate change. © 2014 Blackwell Verlag GmbH.

Hypoplastic left heart syndrome and pulmonary veno-occlusive disease in an infant.

PubMed

D'Souza, Marise; Vergales, Jeffrey; Jayakumar, K Anitha

2013-01-01

This report describes an infant with heterotaxy syndrome and severe hypoplasia of the left heart who presented with profound cyanosis at birth despite a large patent ductus arteriosus. Pulmonary venous return was difficult to demonstrate by echocardiography. Angiography showed total anomalous pulmonary venous return via a plexus that drained through the paravertebral veins and bilateral superior vena cavae. Autopsy confirmed these findings, and histopathology demonstrated severe occlusive changes within the pulmonary veins.

Rodent Abundance and Hantavirus Infection in Protected Area, East-Central Argentina

PubMed Central

Maroli, Malena; Vadell, María Victoria; Padula, Paula

2018-01-01

We captured 3 hantavirus rodent hosts in Otamendi Natural Reserve, Argentina, during 2007–2012. Hantavirus antibodies were found only in Akodon azarae grass mice, mainly in males and old animals. Higher abundance of this species was associated with warm and rainy weather and high water levels, which peaked after a strong El Niño event. PMID:29260665

[Obesity hypoventilation syndrome and pulmonary hypertension. An association little-known in Mexico].

PubMed

Díaz-Domínguez, Ernesto; Rosas-Peralta, Martín; Santos-Martínez, Luis Efrén; Rodríguez-Almendros, Nielzer Armando; Magaña-Serrano, José Antonio; Pérez-Rodríguez, Gilberto

2018-01-01

The obesity hypoventilation syndrome (OHS) refers to the combination of obesity, daytime hypercapnia and sleep-disordered breathing. Obesity has risen to epidemic proportions in the last three decades in the United States, Mexico and Europe. The OHS is associated with obstructive sleep apnea syndrome in 30%. Without treatment, mortality is 46% at 50 months. So in this paper we analyze the OHS, obesity and pulmonary hypertension, the pathophysiology, clinical presentation and diagnosis as well as the treatment, which is aimed at the correction of sleep-disordered breathing and hypoxemia; although there is little experience with the use of specific pulmonary vasodilator drugs.

Pulmonary manifestations of Birt-Hogg-Dubé syndrome

PubMed Central

Seyama, Kuniaki; McCormack, Francis X.

2015-01-01

Birt-Hogg-Dubé syndrome (BHD) is a rare, autosomal dominant disorder characterized by the development of hair follicle tumors, renal tumors and pulmonary cysts. BHD is caused by heterozygous, predominantly truncating mutations in the folliculin (FLCN) gene located on chromosome 17, which encodes a highly conserved tumor suppressor protein. Although management of renal tumors of low malignant potential is the primary focus of longitudinal care, pulmonary manifestations including cyst formation and spontaneous pneumothorax are among the most common manifestations in BHD. Due to the lack of awareness, there is commonly a delay in the pulmonary diagnosis of BHD and patients are frequently mislabeled as having chronic obstructive lung disease, emphysema or common bullae/blebs. A family history of pneumothorax is present in 35 % of patients with BHD. Certain imaging characteristics of the cysts, including size, basilar and peripheral predominance, perivascular and periseptal localization, and elliptical or lentiform shape can suggest the diagnosis of BHD based on inspection of the chest CT scan alone. Recurrent pneumothoraces are common and early pleurodesis is recommended. A better understanding of role of FLCN in pulmonary cyst formation and long term studies to define the natural history of the pulmonary manifestations of BHD are needed. PMID:23715758

Molecular Phylogeny of Hantaviruses Harbored by Insectivorous Bats in Côte d’Ivoire and Vietnam

PubMed Central

Gu, Se Hun; Lim, Burton K.; Kadjo, Blaise; Arai, Satoru; Kim, Jeong-Ah; Nicolas, Violaine; Lalis, Aude; Denys, Christiane; Cook, Joseph A.; Dominguez, Samuel R.; Holmes, Kathryn V.; Urushadze, Lela; Sidamonidze, Ketevan; Putkaradze, Davit; Kuzmin, Ivan V.; Kosoy, Michael Y.; Song, Jin-Won; Yanagihara, Richard

2014-01-01

The recent discovery of genetically distinct hantaviruses in multiple species of shrews and moles prompted a further exploration of their host diversification by analyzing frozen, ethanol-fixed and RNAlater®-preserved archival tissues and fecal samples from 533 bats (representing seven families, 28 genera and 53 species in the order Chiroptera), captured in Asia, Africa and the Americas in 1981–2012, using RT-PCR. Hantavirus RNA was detected in Pomona roundleaf bats (Hipposideros pomona) (family Hipposideridae), captured in Vietnam in 1997 and 1999, and in banana pipistrelles (Neoromicia nanus) (family Vespertilionidae), captured in Côte d’Ivoire in 2011. Phylogenetic analysis, based on the full-length S- and partial M- and L-segment sequences using maximum likelihood and Bayesian methods, demonstrated that the newfound hantaviruses formed highly divergent lineages, comprising other recently recognized bat-borne hantaviruses in Sierra Leone and China. The detection of bat-associated hantaviruses opens a new era in hantavirology and provides insights into their evolutionary origins. PMID:24784569

Reported Cases of HPS (Hantavirus Pulmonary Syndrome)

MedlinePlus

... Brazil, Chile, Ecuador, Paraguay, Panama and Uruguay and Venezuela. Large outbreaks have been rare and have usually ... Watch RSS ABOUT About CDC Jobs Funding LEGAL Policies Privacy FOIA No Fear Act OIG 1600 Clifton ...

Ecology of rodent-associated hantaviruses in the Southern Cone of South America: Argentina, Chile, Paraguay, and Uruguay.

PubMed

Palma, R Eduardo; Polop, Jaime J; Owen, Robert D; Mills, James N

2012-04-01

Thirteen hantavirus genotypes, associated with at least 12 sigmodontine reservoir rodents, have been recognized in the four countries that represent the Southern Cone of South America. Host-virus relationships are not as well defined as in North America; several Southern Cone hantaviruses appear to share a common host and some viruses do not occur throughout the range of their host. Although hantavirus-host relationships in the Southern Cone are less strictly concordant with the single-host-single-virus pattern reported elsewhere, recent studies suggest that much of the ambiguity may result from an incomplete understanding of host and hantavirus systematics. Although some Southern Cone host species are habitat generalists, some sympatric species are habitat specialists, helping to explain how some strict host-virus pairings may be maintained. In some cases, host population densities were higher in peridomestic habitats and prevalence of hantavirus infection was higher in host populations in peridomestic habitats. Seasonal and multiyear patterns in climate and human disturbance affect host population densities, prevalence of infection, and disease risk to humans. Unusually high hantavirus antibody prevalence in indigenous human populations may be associated with frequent and close contact with host rodents. Ongoing studies are improving our understanding of hantavirus-host ecology and providing tools that may predict human risk.

Hantaviruses induce cell type- and viral species-specific host microRNA expression signatures

PubMed Central

Shin, Ok Sarah; Kumar, Mukesh; Yanagihara, Richard; Song, Jin-Won

2014-01-01

The mechanisms of hantavirus-induced modulation of host cellular immunity remain poorly understood. Recently, microRNAs (miRNAs) have emerged as a class of essential regulators of host immune response genes. To ascertain if differential host miRNA expression toward representative hantavirus species correlated with immune response genes, miRNA expression profiles were analyzed in human endothelial cells, macrophages and epithelial cells infected with pathogenic and nonpathogenic rodent- and shrew-borne hantaviruses. Distinct miRNA expression profiles were observed in a cell type- and viral species-specific pattern. A subset of miRNAs, including miR-151-5p and miR-1973, were differentially expressed between Hantaan virus and Prospect Hill virus. Pathway analyses confirmed that the targets of selected miRNAs were associated with inflammatory responses and innate immune receptor-mediated signaling pathways. Our data suggest that differential immune responses following hantavirus infection may be regulated in part by cellular miRNA through dysregulation of genes critical to the inflammatory process. PMID:24074584

Host switch during evolution of a genetically distinct hantavirus in the American shrew mole (Neurotrichus gibbsii)

PubMed Central

Kang, Hae Ji; Bennett, Shannon N.; Dizney, Laurie; Sumibcay, Laarni; Arai, Satoru; Ruedas, Luis A.; Song, Jin-Won; Yanagihara, Richard

2009-01-01

A genetically distinct hantavirus, designated Oxbow virus (OXBV), was detected in tissues of an American shrew mole (Neurotrichus gibbsii), captured in Gresham, Oregon, in September 2003. Pairwise analysis of full-length S- and M- and partial L-segment nucleotide and amino acid sequences of OXBV indicated low sequence similarity with rodent-borne hantaviruses. Phylogenetic analyses using maximum-likelihood and Bayesian methods, and host-parasite evolutionary comparisons, showed that OXBV and Asama virus, a hantavirus recently identified from the Japanese shrew mole (Urotrichus talpoides), were related to soricine shrew-borne hantaviruses from North America and Eurasia, respectively, suggesting parallel evolution associated with cross-species transmission. PMID:19394994

Sjögren's syndrome with multiple cystic lesions and pulmonary arteriovenous fistulae.

PubMed

Taniguchi, Hirokazu; Miwa, Atsuo; Abo, Hitoshi; Demachi, Hiroshi; Izumi, Saburo

2008-01-01

A patient presented with Sjögren's syndrome associated with pulmonary multiple cystic lesions and a pulmonary arteriovenous fistulae. A histological examination of the lungs during the autopsy revealed the stenosis of the bronchiole lumens with hyperplasia of goblet cells, proliferation of smooth muscles in the inner wall of the bronchioli and retention of mucus in the airway lumens. These small airway changes were accompanied with chronic inflammatory changes of the airways in Sjögren's syndrome and led to the formation of cystic lesions via a ball-valve mechanism. Arteriovenous fistulae were situated around the cystic lesions. There may have been a correlation between the formation of the fistulae and cysts, but no mechanism was indicated in the histological findings. This report reveals that chronic inflammatory changes of the airways in Sjögren's syndrome are sufficient to cause the formation of cystic lesions.

Hantavirus Gn and Gc glycoproteins self-assemble into virus-like particles.

PubMed

Acuña, Rodrigo; Cifuentes-Muñoz, Nicolás; Márquez, Chantal L; Bulling, Manuela; Klingström, Jonas; Mancini, Roberta; Lozach, Pierre-Yves; Tischler, Nicole D

2014-02-01

How hantaviruses assemble and exit infected cells remains largely unknown. Here, we show that the expression of Andes (ANDV) and Puumala (PUUV) hantavirus Gn and Gc envelope glycoproteins lead to their self-assembly into virus-like particles (VLPs) which were released to cell supernatants. The viral nucleoprotein was not required for particle formation. Further, a Gc endodomain deletion mutant did not abrogate VLP formation. The VLPs were pleomorphic, exposed protrusions and reacted with patient sera.

Ectopic ACTH syndrome caused by pulmonary carcinoid tumourlets.

PubMed

Povedano, S T; Pastor, C V; Seoane, C P; Reina, L J; Moreno, M A; Ortega, R P; López-Rubio, F; López, P B

2001-06-01

The differential diagnosis of Cushing's syndrome is a major challenge to clinical endocrinologists, especially those infrequent cases referred to as occult ectopic ACTH syndromes. Although bronchial carcinoids are well known to be a cause of Cushing's syndrome due to ectopic ACTH secretion, very few cases of carcinoid tumourlets causing an ACTH ectopic syndrome have been reported, and their origin remains controversial. For some authors, tumourlets and typical carcinoids represent distinct pathological entities, whilst others hold that tumourlets are merely microscopic carcinoid tumours. We report a patient with an aggressive Cushing's syndrome that required bilateral adrenalectomy, diagnosed 22 years before a 3-cm lung nodule became apparent on routine chest X-ray. The biopsy after lung surgery revealed a typical peripheral bronchial carcinoid surrounded by tumourlets. Both tumourlets and carcinoid tumour showed strongly positive ACTH immunostaining. Recently, Arioglu et al. (1998) reported a case of Cushing's syndrome caused by pulmonary carcinoid tumourlets, concluding that this entity should be considered in the differential diagnosis of occult ectopic ACTH syndrome. Furthermore, we consider that the carcinoid tumourlets found in our patient, were the initial source of ACTH, leading to Cushing's syndrome with a rapid onset, and that a loss of cell proliferation control in one of such tumourlets many years later, could have resulted in the development of a typical carcinoid tumour, reinforcing the theory of a common origin of these lesions.

Pulmonary accumulation of polymorphonuclear leukocytes in the adult respiratory distress syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Powe, J.E.; Short, A.; Sibbald, W.J.

1982-11-01

The polymorphonuclear leukocyte (PMN) plays an integral role in the development of permeability pulmonary edema associated with the adult respiratory distress syndrome (ARDS). This report describes 3 patients with ARDS secondary to systemic sepsis who demonstrated an abnormal diffuse accumulation of Indium (/sup 111/In)-labeled PMNs in their lungs, without concomitant clinical or laboratory evidence of a primary chest infection. In one patient, the accumulation of the pulmonary activity during an initial pass suggested that this observation was related to diffuse leukoaggregation within the pulmonary microvasculature. A 4th patient with ARDS was on high-dose corticosteroids at the time of a similarmore » study, and showed no pulmonary accumulation of PMNs, suggesting a possible reason for the reported beneficial effect of corticosteroids in human ARDS.« less

Prediction of Peromyscus maniculatus (deer mouse) population dynamics in Montana, USA, using satellite-driven vegetation productivity and weather data

Treesearch

Rachel A. Loehman; Joran Elias; Richard J. Douglass; Amy J. Kuenzi; James N. Mills; Kent Wagoner

2012-01-01

Deer mice (Peromyscus maniculatus) are the main reservoir host for Sin Nombre virus, the primary etiologic agent of hantavirus pulmonary syndrome in North America. Sequential changes in weather and plant productivity (trophic cascades) have been noted as likely catalysts of deer mouse population irruptions, and monitoring and modeling of these phenomena may allow for...

Tula hantavirus NSs protein accumulates in the perinuclear area in infected and transfected cells.

PubMed

Virtanen, Jussi Oskari; Jääskeläinen, Kirsi Maria; Djupsjöbacka, Janica; Vaheri, Antti; Plyusnin, Alexander

2010-01-01

The small RNA segment of some hantaviruses (family Bunyaviridae) encodes two proteins: the nucleocapsid protein and, in an overlapping reading frame, a non-structural (NSs) protein. The hantavirus NSs protein, like those of orthobunya- and phleboviruses, counteracts host innate immunity. Here, for the first time, the NSs protein of a hantavirus (Tula virus) has been observed in infected cells and shown to localize in the perinuclear area. Transiently expressed NSs protein showed similar localization, although the kinetics was slightly different, suggesting that to reach its proper location in the infected cell, the NSs protein does not have to cooperate with other viral proteins.

Hantavirus surveillance and genetic diversity targeting small mammals at Camp Humphreys, a US military installation and new expansion site, Republic of Korea

PubMed Central

Klein, Terry A.; Chong, Sung-Tae; Nunn, Peter V.; Kim, Jeong-Ah; Lee, Seung-Ho; No, Jin Sun; Song, Jin-Won

2017-01-01

Small mammal surveillance was conducted (2008–2010, 2012) at Camp (Cp) Humphreys, a US Army installation and new expansion site, Republic of Korea (ROK), to identify hemorrhagic fever with renal syndrome health threats to US military/civilian populations during its ongoing expansion phase. Small mammals were collected using Sherman live capture traps and transported to Korea University where they were euthanized, tissues removed, and assayed to determine hantavirus IgG antibody-positive and hantavirus-positive rates by RT-PCR. A total of 2,364 small mammals were captured over 11,300 trap nights (capture rate = 20.92%). Apodemus agrarius was the most commonly collected (76.65%), with capture rates of 9.62% and 21.70% for Cp Humphreys and the expansion site, respectively. Overall, Hantaan virus (HTNV) IgG antibody-positive (Ab+) rate for A. agrarius was 2.15% (39/1,812). A total of 5.43% (10/184) Crocidura lasiura, 0.79% (2/254) Microtus fortis and 2.44% (1/41) Micromys minutus were serologically IgG Ab+ for hantaviruses. HTNV-specific RT-PCR demonstrated that 28.2% (11/39) HTNV Ab+ A. agrarius harbored the 328-nt sequence of the GC glycoprotein-encoding M segment of HTNV. Among them, the whole genome sequences of 3 HTNV strains were obtained by conventional RT-PCR and Rapid Amplification cDNA Ends PCR. Phylogenetic analyses of the HTNV strains from Cp Humphreys and the expansion site, Pyeongtaek, show a greater diversity of rodent-borne hantaviruses compared to HTNV previously identified in Gyeonggi province of the ROK. Thus, this study provides significant insights for raising HFRS threat awareness, analysis, and risk reduction strategies in southern Gyeonggi province. PMID:28448595

Hantavirus Gn and Gc Glycoproteins Self-Assemble into Virus-Like Particles

PubMed Central

Acuña, Rodrigo; Cifuentes-Muñoz, Nicolás; Márquez, Chantal L.; Bulling, Manuela; Klingström, Jonas; Mancini, Roberta; Lozach, Pierre-Yves

2014-01-01

How hantaviruses assemble and exit infected cells remains largely unknown. Here, we show that the expression of Andes (ANDV) and Puumala (PUUV) hantavirus Gn and Gc envelope glycoproteins lead to their self-assembly into virus-like particles (VLPs) which were released to cell supernatants. The viral nucleoprotein was not required for particle formation. Further, a Gc endodomain deletion mutant did not abrogate VLP formation. The VLPs were pleomorphic, exposed protrusions and reacted with patient sera. PMID:24335294

Clinician gestalt estimate of pretest probability for acute coronary syndrome and pulmonary embolism in patients with chest pain and dyspnea.

PubMed

Kline, Jeffrey A; Stubblefield, William B

2014-03-01

Pretest probability helps guide diagnostic testing for patients with suspected acute coronary syndrome and pulmonary embolism. Pretest probability derived from the clinician's unstructured gestalt estimate is easier and more readily available than methods that require computation. We compare the diagnostic accuracy of physician gestalt estimate for the pretest probability of acute coronary syndrome and pulmonary embolism with a validated, computerized method. This was a secondary analysis of a prospectively collected, multicenter study. Patients (N=840) had chest pain, dyspnea, nondiagnostic ECGs, and no obvious diagnosis. Clinician gestalt pretest probability for both acute coronary syndrome and pulmonary embolism was assessed by visual analog scale and from the method of attribute matching using a Web-based computer program. Patients were followed for outcomes at 90 days. Clinicians had significantly higher estimates than attribute matching for both acute coronary syndrome (17% versus 4%; P<.001, paired t test) and pulmonary embolism (12% versus 6%; P<.001). The 2 methods had poor correlation for both acute coronary syndrome (r(2)=0.15) and pulmonary embolism (r(2)=0.06). Areas under the receiver operating characteristic curve were lower for clinician estimate compared with the computerized method for acute coronary syndrome: 0.64 (95% confidence interval [CI] 0.51 to 0.77) for clinician gestalt versus 0.78 (95% CI 0.71 to 0.85) for attribute matching. For pulmonary embolism, these values were 0.81 (95% CI 0.79 to 0.92) for clinician gestalt and 0.84 (95% CI 0.76 to 0.93) for attribute matching. Compared with a validated machine-based method, clinicians consistently overestimated pretest probability but on receiver operating curve analysis were as accurate for pulmonary embolism but not acute coronary syndrome. Copyright © 2013 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.

Rodent Species Distribution and Hantavirus Seroprevalence in Residential and Forested areas of Sarawak, Malaysia.

PubMed

Hamdan, Nur Elfieyra Syazana; Ng, Yee Ling; Lee, Wei Bin; Tan, Cheng Siang; Khan, Faisal Ali Anwarali; Chong, Yee Ling

2017-01-01

Rodents belong to the order Rodentia, which consists of three families in Borneo (i.e., Muridae, Sciuridae and Hystricidae). These include rats, mice, squirrels, and porcupines. They are widespread throughout the world and considered pests that harm humans and livestock. Some rodent species are natural reservoirs of hantaviruses (Family: Bunyaviridae) that can cause zoonotic diseases in humans. Although hantavirus seropositive human sera were reported in Peninsular Malaysia in the early 1980s, information on their infection in rodent species in Malaysia is still lacking. The rodent populations in residential and forested areas in Sarawak were sampled. A total of 108 individuals from 15 species of rodents were collected in residential ( n = 44) and forested ( n = 64) areas. The species diversity of rodents in forested areas was significantly higher (H = 2.2342) compared to rodents in residential areas (H = 0.64715) ( p < 0.001 of Zar-t test based on the Shannon index). Rattus rattus and Sundamys muelleri were present at high frequencies in both localities. An enzyme-linked immunosorbent assay (ELISA) showed that hantavirus-targeting antibodies were absent from 53 tested serum samples. This is the first report of hantavirus seroprevalence surveillance in rodent populations in Sarawak, East Malaysia. The results suggested that hantavirus was not circulating in the studied rodent populations in Sarawak, or it was otherwise at a low prevalence that is below the detection threshold. It is important to remain vigilant because of the zoonotic potential of this virus and its severe disease outcome. Further studies, such as molecular detection of viral genetic materials, are needed to fully assess the risk of hantavirus infection in rodents and humans in this region of Malaysia.

Rodent Species Distribution and Hantavirus Seroprevalence in Residential and Forested areas of Sarawak, Malaysia

PubMed Central

Hamdan, Nur Elfieyra Syazana; Ng, Yee Ling; Lee, Wei Bin; Tan, Cheng Siang; Khan, Faisal Ali Anwarali; Chong, Yee Ling

2017-01-01

Rodents belong to the order Rodentia, which consists of three families in Borneo (i.e., Muridae, Sciuridae and Hystricidae). These include rats, mice, squirrels, and porcupines. They are widespread throughout the world and considered pests that harm humans and livestock. Some rodent species are natural reservoirs of hantaviruses (Family: Bunyaviridae) that can cause zoonotic diseases in humans. Although hantavirus seropositive human sera were reported in Peninsular Malaysia in the early 1980s, information on their infection in rodent species in Malaysia is still lacking. The rodent populations in residential and forested areas in Sarawak were sampled. A total of 108 individuals from 15 species of rodents were collected in residential (n = 44) and forested ( n = 64) areas. The species diversity of rodents in forested areas was significantly higher (H = 2.2342) compared to rodents in residential areas (H = 0.64715) (p < 0.001 of Zar-t test based on the Shannon index). Rattus rattus and Sundamys muelleri were present at high frequencies in both localities. An enzyme-linked immunosorbent assay (ELISA) showed that hantavirus-targeting antibodies were absent from 53 tested serum samples. This is the first report of hantavirus seroprevalence surveillance in rodent populations in Sarawak, East Malaysia. The results suggested that hantavirus was not circulating in the studied rodent populations in Sarawak, or it was otherwise at a low prevalence that is below the detection threshold. It is important to remain vigilant because of the zoonotic potential of this virus and its severe disease outcome. Further studies, such as molecular detection of viral genetic materials, are needed to fully assess the risk of hantavirus infection in rodents and humans in this region of Malaysia. PMID:28228923

Co-circulation of Soricid- and Talpid-borne Hantaviruses in Poland

PubMed Central

Gu, Se Hun; Hejduk, Janusz; Markowski, Janusz; Kang, Hae Ji; Markowski, Marcin; Połatyńska, Małgorzata; Sikorska, Beata; Liberski, Paweł P.; Yanagihara, Richard

2014-01-01

Previously, we reported the discovery of a genetically distinct hantavirus, designated Boginia virus (BOGV), in the Eurasian water shrew (Neomys fodiens), as well as the detection of Seewis virus (SWSV) in the Eurasian common shrew (Sorex araneus), in central Poland. In this expanded study of 133 shrews and 69 moles captured during 2010–2013 in central and southeastern Poland, we demonstrate the co-circulation of BOGV in the Eurasian water shrew and SWSV in the Eurasian common shrew, Eurasian pygmy shrew (Sorex minutus) and Mediterranean water shrew (Neomys anomalus). In addition, we found high prevalence of Nova virus (NVAV) infection in the European mole (Talpa europaea), with evidence of NVAV RNA in heart, lung, liver, kidney, spleen and intestine. The nucleotide and amino acid sequence variation of the L segment among the SWSV strains was 0–18.8% and 0–5.4%, respectively. And for the 38 NVAV strains from European moles captured in Huta Dłutowska, the L-segment genetic similarity ranged from 94.1–100% at the nucleotide level and 96.3–100% at the amino acid level. Phylogenetic analyses showed geographic-specific lineages of SWSV and NVAV in Poland, not unlike that of rodent-borne hantaviruses, suggesting long-standing host-specific adaptation. The co-circulation and distribution of BOGV, SWSV and NVAV in Poland parallels findings of multiple hantavirus species coexisting in their respective rodent reservoir species elsewhere in Europe. Also, the detection of SWSV in three syntopic shrew species resembles spill over events observed among some rodent-borne hantaviruses. PMID:25445646

Co-circulation of soricid- and talpid-borne hantaviruses in Poland.

PubMed

Gu, Se Hun; Hejduk, Janusz; Markowski, Janusz; Kang, Hae Ji; Markowski, Marcin; Połatyńska, Małgorzata; Sikorska, Beata; Liberski, Paweł P; Yanagihara, Richard

2014-12-01

Previously, we reported the discovery of a genetically distinct hantavirus, designated Boginia virus (BOGV), in the Eurasian water shrew (Neomys fodiens), as well as the detection of Seewis virus (SWSV) in the Eurasian common shrew (Sorex araneus), in central Poland. In this expanded study of 133 shrews and 69 moles captured during 2010-2013 in central and southeastern Poland, we demonstrate the co-circulation of BOGV in the Eurasian water shrew and SWSV in the Eurasian common shrew, Eurasian pygmy shrew (Sorex minutus) and Mediterranean water shrew (Neomys anomalus). In addition, we found high prevalence of Nova virus (NVAV) infection in the European mole (Talpa europaea), with evidence of NVAV RNA in heart, lung, liver, kidney, spleen and intestine. The nucleotide and amino acid sequence variation of the L segment among the SWSV strains was 0-18.8% and 0-5.4%, respectively. And for the 38 NVAV strains from European moles captured in Huta Dłutowska, the L-segment genetic similarity ranged from 94.1%-100% at the nucleotide level and 96.3%-100% at the amino acid level. Phylogenetic analyses showed geographic-specific lineages of SWSV and NVAV in Poland, not unlike that of rodent-borne hantaviruses, suggesting long-standing host-specific adaptation. The co-circulation and distribution of BOGV, SWSV and NVAV in Poland parallels findings of multiple hantavirus species co-existing in their respective rodent reservoir species elsewhere in Europe. Also, the detection of SWSV in three syntopic shrew species resembles spill over events observed among some rodent-borne hantaviruses. Copyright © 2014 Elsevier B.V. All rights reserved.

An enigmatic case presentation of Budd-Chiari syndrome with pulmonary embolism: An unusual syndrome with an uncommon complication.

PubMed

Al-Sharydah, A M; Al-Abdulwahhab, A H; Abu AlOla, H A

2018-05-03

In patients with a hypercoagulable state, such as patients with pulmonary embolism and/or Budd-Chiari syndrome, the complications from multiple gene mutations are more numerous than those from a single mutation. The authors present a woman with no major prior medical history who presented with pulmonary embolism and Budd-Chiari syndrome; this enigmatic co-occurrence has never been solely reported without underlying aetiology in a patient without prior medical conditions. A 20-year-old female presented to the emergency room complaining of a sudden onset of acute epigastric abdominal pain lasting for approximately 2 h. The patient's liver enzymes were severely elevated. Computed tomography of her abdomen showed thrombosed hepatic veins as well as supra-hepatic and hepatic portions of the inferior vena cava. She was becoming progressively hypotensive despite supplying intravenous fluid. Consequently, the patient received a contrast chest CT, which revealed the presence of acute pulmonary embolism; to confirm the diagnosis of a perfusion abnormality with normal ventilation, a clear radiograph in that region was obtained, denoting a V/Q study mismatch. Many details regarding the enigmatic mechanism behind the appearance of such a thrombotic co-occurrence in our patient are unclear. Since the anticardiolipin antibody IgG and IgM serum levels were normal, blood eosinophil count was persistently normal, and no signs of autoimmune disease were found, the diagnosis of autoimmune disease in the case under discussion is unlikely. Adding pulmonary embolism to the list of complications associated with Budd-Chiari syndrome is highly suggested, regardless of having predisposing condition(s). Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

[Prevalence of antibodies to hantavirus among hemodialysis patients with end-stage renal failure in Kaunas and its district].

PubMed

Dargevicius, Arvydas; Petraityte, Rasa; Sribikiene, Birute; Sileikiene, Elvyra; Razukeviciene, Loreta; Ziginskiene, Edita; Vorobjoviene, Rita; Razanskiene, Ausra; Sasnauskas, Kestutis; Bumblyte, Inga Arūne; Kuzminskis, Vytautas

2007-01-01

The objective of this study was to investigate the prevalence of antibodies to hantaviruses among hemodialysis patients with end-stage renal failure in Kaunas and its district. Serums of 218 patients from four dialysis centers of Kaunas district were tested by using the immunoglobulin G antibody-capture enzyme-linked immunosorbent assay (ELISA). The reactivity of ELISA-positive sera was proven in Western blot tests using various hantavirus recombinant nucleocapsid proteins. The yeast-expressed nucleocapsid proteins were used for testing. Antibodies against Dobrava/Hantaan and Puumala hantaviruses were found in 16 patients (seroprevalence 7.4%). Most of the sera were positive for Dobrava hantavirus (81%). The ratio of males to females was 1.2:1. Seroprevalence was significantly higher in older patients. Results indicate that antibodies to two hantaviruses (Dobrava/Hantaan virus and Puumala virus) are prevalent among hemodialysis patients in Kaunas district with approximately the same seroprevalence as in neighboring countries.

Birt-Hogg-Dubé syndrome. State-of-the-art review with emphasis on pulmonary involvement.

PubMed

Dal Sasso, Aline Amaral; Belém, Luciana Camara; Zanetti, Gláucia; Souza, Carolina Althoff; Escuissato, Dante Luiz; Irion, Klaus Loureiro; Guimarães, Marcos Duarte; Marchiori, Edson

2015-03-01

Birt-Hogg-Dubé syndrome (BHDS) is a rare, inherited autosomal-dominant disorder characterized by the development of cutaneous lesions, renal tumors, pulmonary cysts, and spontaneous pneumothorax. The gene responsible for BHDS is located on the short arm of chromosome 17 (17p11.2) and codes for the protein folliculin, which is believed to be an oncogene suppressor protein. We reviewed currently published literature on the main characteristics of BHDS. Pulmonary cysts and spontaneous pneumothorax are often the presenting manifestations that lead to a final diagnosis in family members affected by the syndrome. Certain imaging characteristics of pulmonary cysts, including size and location, can suggest the diagnosis of BHDS based on chest computed tomography alone. The main concern in patients with BHDS is the increased risk of renal carcinoma. The aim of this review is to describe the main pathological, clinical, and imaging aspects of BHDS, ranging from its genetic basis to treatment, with emphasis on pulmonary involvement. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Myositis, polysynovitis and pulmonary fibrosis: anti-Jo-1 syndrome].

PubMed

Perrenoud, F G; Van Lindhoudt, D; Ochsner, F; Janzer, R C; Ott, H

1996-01-27

Polymyositis/dermatomyositis are rare autoimmune diseases. Classification is usually performed according to the criteria of Bohan and Peter. The occurrence of myositis-specific autoantibodies has recently been described in inflammatory myopathies. Approximately half of the patients can now be classified by these specific autoantibodies. Several of these autoantibodies (anti-aminoacyl-tRNA synthetases, anti-SRP, anti-Mi2) are strongly associated with the clinical presentation. We may expect that in the future different subsets of these diseases will be increasingly identified by serum antibodies. We report on a patient with myopathy, pulmonary fibrosis and polysynovitis, a typical clinical presentation of the anti-Jo1 syndrome (anti-synthetase syndrome).

[Pulmonary hypertension associated with congenital heart disease and Eisenmenger syndrome].

PubMed

Calderón-Colmenero, Juan; Sandoval Zárate, Julio; Beltrán Gámez, Miguel

2015-01-01

Pulmonary arterial hypertension is a common complication of congenital heart disease (CHD). Congenital cardiopathies are the most frequent congenital malformations. The prevalence in our country remains unknown, based on birthrate, it is calculated that 12,000 to 16,000 infants in our country have some cardiac malformation. In patients with an uncorrected left-to-right shunt, increased pulmonary pressure leads to vascular remodeling and endothelial dysfunction secondary to an imbalance in vasoactive mediators which promotes vasoconstriction, inflammation, thrombosis, cell proliferation, impaired apotosis and fibrosis. The progressive rise in pulmonary vascular resistance and increased pressures in the right heart provocated reversal of the shunt may arise with the development of Eisenmenger' syndrome the most advanced form de Pulmonary arterial hypertension associated with congenital heart disease. The prevalence of Pulmonary arterial hypertension associated with CHD has fallen in developed countries in recent years that is not yet achieved in developing countries therefore diagnosed late as lack of hospital infrastructure and human resources for the care of patients with CHD. With the development of targeted medical treatments for pulmonary arterial hypertension, the concept of a combined medical and interventional/surgical approach for patients with Pulmonary arterial hypertension associated with CHD is a reality. We need to know the pathophysiological factors involved as well as a careful evaluation to determine the best therapeutic strategy. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Pulmonary eosinophilia.

PubMed

Campos, Luiz Eduardo Mendes; Pereira, Luiz Fernando Ferreira

2009-06-01

Pulmonary eosinophilia comprises a heterogeneous group of diseases defined by eosinophilia in pulmonary infiltrates (bronchoalveolar lavage fluid) or in tissue (lung biopsy specimens). Although the inflammatory infiltrate is composed of macrophages, lymphocytes, neutrophils and eosinophils, eosinophilia is an important marker for the diagnosis and treatment. Clinical and radiological presentations can include simple pulmonary eosinophilia, chronic eosinophilic pneumonia, acute eosinophilic pneumonia, allergic bronchopulmonary aspergillosis and pulmonary eosinophilia associated with a systemic disease, such as in Churg-Strauss syndrome and hypereosinophilic syndrome. Asthma is frequently concomitant and can be a prerequisite, as in allergic bronchopulmonary aspergillosis and Churg-Strauss syndrome. In diseases with systemic involvement, the skin, the heart and the nervous system are the most affected organs. The radiological presentation can be typical, or at least suggestive, of one of three types of pulmonary eosinophilia: chronic eosinophilic pneumonia, acute eosinophilic pneumonia and allergic bronchopulmonary aspergillosis. The etiology of pulmonary eosinophilia can be either primary (idiopathic) or secondary, due to known causes, such as drugs, parasites, fungal infection, mycobacterial infection, irradiation and toxins. Pulmonary eosinophilia can be also associated with diffuse lung diseases, connective tissue diseases and neoplasia.

Population dynamics of the deer mouse (Peromyscus maniculatus) and Sin Nombre Virus, California Channel Islands

USGS Publications Warehouse

Graham, T.B.; Chomel, B.B.

1997-01-01

Hantavirus pulmonary syndrome, first documented in 1993, is caused by Sin Nombre virus (SNV), which is carried by the Peromyscus species. In 1994, high SNV antibody prevalence was identified in deer mice from two California Channel Islands. We sampled two locations on three islands to estimate mouse population density and SNV prevalence. Population flux and SNV prevalence appear to vary independently.

Indirect Immunofluorescence Assay for the Simultaneous Detection of Antibodies against Clinically Important Old and New World Hantaviruses

PubMed Central

Lederer, Sabine; Lattwein, Erik; Hanke, Merle; Sonnenberg, Karen; Stoecker, Winfried; Lundkvist, Åke; Vaheri, Antti; Vapalahti, Olli; Chan, Paul K. S.; Feldmann, Heinz; Dick, Daryl; Schmidt-Chanasit, Jonas; Padula, Paula; Vial, Pablo A.; Panculescu-Gatej, Raluca; Ceianu, Cornelia; Heyman, Paul; Avšič-Županc, Tatjana; Niedrig, Matthias

2013-01-01

In order to detect serum antibodies against clinically important Old and New World hantaviruses simultaneously, multiparametric indirect immunofluorescence assays (IFAs) based on biochip mosaics were developed. Each of the mosaic substrates consisted of cells infected with one of the virus types Hantaan (HTNV), Puumala (PUUV), Seoul (SEOV), Saaremaa (SAAV), Dobrava (DOBV), Sin Nombre (SNV) or Andes (ANDV). For assay evaluation, serum IgG and IgM antibodies were analyzed using 184 laboratory-confirmed hantavirus-positive sera collected at six diagnostic centers from patients actively or previously infected with the following hantavirus serotypes: PUUV (Finland, n = 97); SEOV (China, n = 5); DOBV (Romania, n = 7); SNV (Canada, n = 23); ANDV (Argentina and Chile, n = 52). The control panel comprised 89 sera from healthy blood donors. According to the reference tests, all 184 patient samples were seropositive for hantavirus-specific IgG (n = 177; 96%) and/or IgM (n = 131; 72%), while all control samples were tested negative. In the multiparametric IFA applied in this study, 183 (99%) of the patient sera were IgG and 131 (71%) IgM positive (accordance with the reference tests: IgG, 96%; IgM, 93%). Overall IFA sensitivity for combined IgG and IgM analysis amounted to 100% for all serotypes, except for SNV (96%). Of the 89 control sera, 2 (2%) showed IgG reactivity against the HTNV substrate, but not against any other hantavirus. Due to the high cross-reactivity of hantaviral nucleocapsid proteins, endpoint titrations were conducted, allowing serotype determination in >90% of PUUV- and ANDV-infected patients. Thus, multiparametric IFA enables highly sensitive and specific serological diagnosis of hantavirus infections and can be used to differentiate PUUV and ANDV infection from infections with Murinae-borne hantaviruses (e.g. DOBV and SEOV). PMID:23593524

Adler hantavirus, a new genetic variant of Tula virus identified in Major's pine voles (Microtus majori) sampled in southern European Russia.

PubMed

Tkachenko, Evgeniy A; Witkowski, Peter T; Radosa, Lukas; Dzagurova, Tamara K; Okulova, Nataliya M; Yunicheva, Yulia V; Vasilenko, Ludmila; Morozov, Vyacheslav G; Malkin, Gennadiy A; Krüger, Detlev H; Klempa, Boris

2015-01-01

Although at least 30 novel hantaviruses have been recently discovered in novel hosts such as shrews, moles and even bats, hantaviruses (family Bunyaviridae, genus Hantavirus) are primarily known as rodent-borne human pathogens. Here we report on identification of a novel hantavirus variant associated with a rodent host, Major's pine vole (Microtus majori). Altogether 36 hantavirus PCR-positive Major's pine voles were identified in the Krasnodar region of southern European Russia within the years 2008-2011. Initial partial L-segment sequence analysis revealed novel hantavirus sequences. Moreover, we found a single common vole (Microtusarvalis) infected with Tula virus (TULV). Complete S- and M-segment coding sequences were determined from 11 Major's pine voles originating from 8 trapping sites and subjected to phylogenetic analyses. The data obtained show that Major's pine vole is a newly recognized hantavirus reservoir host. The newfound virus, provisionally called Adler hantavirus (ADLV), is closely related to TULV. Based on amino acid differences to TULV (5.6-8.2% for nucleocapsid protein, 9.4-9.5% for glycoprotein precursor) we propose to consider ADLV as a genotype of TULV. Occurrence of ADLV and TULV in the same region suggests that ADLV is not only a geographical variant of TULV but a host-specific genotype. High intra-cluster nucleotide sequence variability (up to 18%) and geographic clustering indicate long-term presence of the virus in this region. Copyright © 2014. Published by Elsevier B.V.

Chronic fibrosing pulmonary aspergillosis: a cause of 'destroyed lung' syndrome.

PubMed

Kosmidis, Chris; Newton, Pippa; Muldoon, Eavan G; Denning, David W

2017-04-01

Chronic pulmonary aspergillosis (CPA) has substantial impact on quality of life. A subset of patients develops significant pulmonary fibrosis, identified either on biopsy or radiologically. The term chronic fibrosing pulmonary aspergillosis (CFPA) has been suggested. We describe 11 patients with CFPA referred to our centre. Mean age was 58.5 years and five were male. In nine, fibrosis was already evident on presentation, while in two it developed 3 and 6 years later. The predominant radiological feature was extensive or complete involvement of the entire lung, with minimal contralateral involvement. All patients received prolonged antifungal treatment. Two patients had surgical treatment; both developed post-operative complications. The contralateral lung remained free of significant disease in all but three patients. CFPA is a rare complication of CPA that is usually evident on presentation, but may develop after years in patients not on antifungals. Fibrosis resembles the 'destroyed lung' syndrome described after treated tuberculosis.

Molecular phylogeny of a genetically divergent hantavirus harbored by the Geoffroy's rousette (Rousettus amplexicaudatus), a frugivorous bat species in the Philippines.

PubMed

Arai, Satoru; Taniguchi, Satoshi; Aoki, Keita; Yoshikawa, Yasuhiro; Kyuwa, Shigeru; Tanaka-Taya, Keiko; Masangkay, Joseph S; Omatsu, Tsutomu; Puentespina, Roberto; Watanabe, Shumpei; Alviola, Phillip; Alvarez, James; Eres, Eduardo; Cosico, Edison; Quibod, Ma Niña Regina M; Morikawa, Shigeru; Yanagihara, Richard; Oishi, Kazunori

2016-11-01

The recent discovery of genetically distinct hantaviruses in multiple species of shrews and moles (order Eulipotyphla, families Soricidae and Talpidae) prompted a further exploration of their host diversification and geographic distribution by analyzing lung tissues from 376 fruit bats representing six genera (order Chiroptera, suborder Yinpterochiroptera, family Pteropodidae), collected in the Republic of the Philippines during 2008 to 2013. Hantavirus RNA was detected by RT-PCR in one of 15 Geoffroy's rousettes (Rousettus amplexicaudatus), captured in Quezon Memorial National Park on Luzon Island in 2009. Phylogenetic analyses of the S, M and L segments, using maximum-likelihood and Bayesian methods, showed that the newfound hantavirus, designated Quezon virus (QZNV), shared a common ancestry with hantaviruses hosted by insectivorous bats, in keeping with their evolutionary relationships and suggests that ancestral bats may have served as the early or original mammalian hosts of primordial hantaviruses. As the first hantavirus detected in a megabat or flying fox species, QZNV extends our knowledge about the reservoir host range. Copyright © 2016 Elsevier B.V. All rights reserved.

Rodent-borne infectious disease outbreaks after flooding disasters: Epidemiology, management, and prevention.

PubMed

Diaz, James H

2015-01-01

To alert clinicians to the climatic conditions that can precipitate outbreaks of the rodent-borne infectious diseases most often associated with flooding disasters, leptospirosis (LS), and the Hantavirus-caused diseases, hemorrhagic fever with renal syndrome (HFRS) and Hantavirus pulmonary syndrome (HPS); to describe the epidemiology and presenting clinical manifestations and outcomes of these rodent-borne infectious diseases; and to recommend both prophylactic therapies and effective control and prevention strategies for rodent-borne infectious diseases. Internet search engines, including Google®, Google Scholar®, Pub Med, Medline, and Ovid, were queried with the key words as search terms to examine the latest scientific articles on rodent-borne infectious disease outbreaks in the United States and worldwide to describe the epidemiology and presenting clinical manifestations and outcomes of LS and Hantavirus outbreaks. Not applicable. Not applicable. Not applicable. Rodent-borne infectious disease outbreaks following heavy rainfall and flooding disasters. Heavy rainfall encourages excessive wild grass seed production that supports increased outdoor rodent population densities; and flooding forces rodents from their burrows near water sources into the built environment and closer to humans. Healthcare providers should maintain high levels of suspicion for LS in patients developing febrile illnesses after contaminated freshwater exposures following heavy rainfall, flooding, and even freshwater recreational events; and for Hantavirus-caused infectious diseases in patients with hemorrhagic fevers that progress rapidly to respiratory or renal failure following rodent exposures.

Drug-Coated Balloon Angioplasty: A Novel Treatment for Pulmonary Artery In-Stent Stenosis in a Patient with Williams Syndrome.

PubMed

Cohen, Jennifer L; Glickstein, Julie S; Crystal, Matthew A

2017-12-01

A 20-month-old boy with Williams syndrome had undergone multiple surgical and catheter-based interventions for resistant peripheral pulmonary arterial stenoses with eventual bilateral stent placement and conventional balloon angioplasty. He persistently developed suprasystemic right ventricular (RV) pressure. Angioplasty with a drug-coated balloon (DCB) was performed for in-stent restenosis and to remodel his distal pulmonary vessels bilaterally. This resulted in immediate improvement in the in-stent stenosis and resultant decrease in RV pressure. Follow-up catheterization two months later continued to show long-lasting improvement in the in-stent stenosis. We hypothesize that the anti-proliferative effects of DCBs may be of benefit in the arteriopathy associated with Williams syndrome. We report this as a novel use of a DCB in the pulmonary arterial circulation in a patient with Williams syndrome.

Pulmonary Fibrosis in Hermansky–Pudlak Syndrome

PubMed Central

Vicary, Glenn W.; Vergne, Yeidyly; Santiago-Cornier, Alberto; Young, Lisa R.

2016-01-01

Hermansky–Pudlak syndrome (HPS) is a rare autosomal recessive genetic disorder characterized by oculocutaneous albinism and a bleeding diathesis due to platelet dysfunction. More than 50% of cases worldwide are diagnosed on the Caribbean island of Puerto Rico. Genetic testing plays a growing role in diagnosis; however, not all patients with HPS have identified genetic mutations. In Puerto Rico, patients with HPS are often identified shortly after birth by their albinism, although the degree of hypopigmentation is highly variable. Ten subtypes have been described. Patients with HPS-1, HPS-2, and HPS-4 tend to develop pulmonary fibrosis in Puerto Rico; 100% of patients with HPS-1 develop HPS-PF. HPS-PF and idiopathic pulmonary fibrosis are considered similar entities (albeit with distinct causes) because both can show similar histological disease patterns. However, in contrast to idiopathic pulmonary fibrosis, HPS-PF manifests much earlier, often at 30–40 years of age. The progression of HPS-PF is characterized by the development of dyspnea and increasingly debilitating hypoxemia. No therapeutic interventions are currently approved by the U.S. Food and Drug Administration for the treatment of HPS and HPS-PF. However, the approval of two new antifibrotic drugs, pirfenidone and nintedanib, has prompted new interest in identifying drugs capable of reversing or halting the progression of HPS-PF. Thus, lung transplantation remains the only potentially life-prolonging treatment. At present, two clinical trials are recruiting patients with HPS-PF to identify biomarkers for disease progression. Advances in the diagnosis and management of these patients will require the establishment of multidisciplinary centers of excellence staffed by experts in this disease. PMID:27529121

Pirfenidone for the treatment of Hermansky-Pudlak Syndrome pulmonary fibrosis

PubMed Central

O’Brien, Kevin; Troendle, James; Gochuico, Bernadette R.; Markello, Thomas C.; Salas, Jose; Cardona, Hilda; Yao, Jianhua; Bernardini, Isa; Hess, Richard; Gahl, William A.

2013-01-01

Hermansky-Pudlak syndrome (HPS) type is a rare disorder of oculocutaneous albinism, platelet dysfunction, and in some subtypes, fatal pulmonary fibrosis. There is no effective treatment for the pulmonary fibrosis except lung transplantation, but an initial trial using pirfenidone, an anti-fibrotic agent, showed promising results. The current, randomized, placebo-controlled, prospective, double-blind trial investigated the safety and efficacy of pirfenidone for mild to moderate HPS-1 and 4 pulmonary fibrosis. Subjects were evaluated every 4 months at the National Institutes of Health Clinical Center, and the primary outcome parameter was change in forced vital capacity using repeated measures analysis with random coefficients. Thirty-five subjects with HPS-1 pulmonary fibrosis were enrolled during a 4-year interval; 23 subjects received pirfenidone and 12 received placebo. Four subjects withdrew from the trial, 3 subjects died, and 10 serious adverse events were reported. Both groups experienced similar side effects, especially gastroesophageal reflux. Interim analysis of the primary outcome parameter, performed 12 months after 30 patients were enrolled, showed no statistical difference between the placebo and pirfenidone groups, and the study was stopped due to futility. There were no significant safety concerns. Other clinical trials are indicated to identify single or multiple drug regimens that may be effective in treatment for progressive HPS-1 pulmonary fibrosis. PMID:21420888

Genovariation Study of Hantavirus in Main Endemic Areas of Hemorrhagic Fever with Renal Syndrome in Hebei Province, China.

PubMed

Li, Qi; Cai, Yanan; Wei, Yamei; Han, Xu; Han, Zhanying; Zhang, Yanbo; Qi, Shunxiang; Xu, Yonggang

2016-01-01

Hemorrhagic fever with renal syndrome (HFRS) is an important infectious disease in Hebei Province. At present, cases from the northeast regions of the province account for >80% of the total incidences. However, studies that examine the region-specific genetic variations of the Hantavirus (HV), the causative pathogen for HFRS, have been lacking. Rodents were collected in northeast Hebei Province from 2004 to 2013, and the HV strains used in this study were isolated in 1993. Lung tissues were isolated from the rodents and HV antigen was detected by indirect immunofluorescence. The M1 and M2 fragments of HV M region were amplified by reverse transcription polymerase chain reaction (RT-PCR), cloned into pMDl9-T vector, sequenced and compared with representative standard stains for homology and phylogenetic analysis. A total of 21 samples of HV antigen-positive were collected. Real-time PCR analysis revealed that the 19 rodent lungs and two HV strains were positive for the SEO virus. 11 samples were chosen to sequence, and they shared 95.8%-99.8% in nucleotide homology, and 83.6%-99.2% when compared to the standard strains of SEO virus. Phylogenetic analysis demonstrated that all strains were grouped into the same S3 subtype. SEO was the major epidemic genotype of HV in the main HFRS endemic areas in Hebei Province, and S3 was the major subtype. There was minor genetic variation in HV over short term periods, while long term variations were higher.

Pulmonary disease at autopsy in patients with the acquired immunodeficiency syndrome.

PubMed

Wallace, J M; Hannah, J B

1988-08-01

To characterize the postmortem pulmonary disease and analyze the effectiveness of antemortem diagnosis, we examined the clinical records and autopsy material from 54 patients who died of the acquired immunodeficiency syndrome. At autopsy, all patients had pulmonary disease. One or more specific diagnoses were made in 53, including opportunistic infection, nonopportunistic infection, and Kaposi's sarcoma. Multiple postmortem pulmonary diagnoses were established in 37. Respiratory failure was the most common cause of death. Of the 97 pulmonary disorders discovered at autopsy, only 31 were diagnosed before death. The frequency with which infections were diagnosed during life varied according to the organism, and was significantly higher for Pneumocystis carinii than for cytomegalovirus or bacterial agents. Pulmonary Kaposi's sarcoma was diagnosed in only 7% of patients with autopsy documentation. The yield of diagnostic procedures also varied according to the disease present. Sputum culture was relatively effective in detecting Cryptococcus neoformans and Mycobacterium avium-intracellulare, fiber-optic bronchoscopy was extremely useful for diagnosing P Carinii, and one or more diagnoses were provided in 4 of 7 patients who underwent thoracotomy, but significant disease including cytomegalovirus infection and pulmonary Kaposi's sarcoma was frequently missed. Although the spectrum of lung disease found at autopsy is similar to that observed during life, the frequency of some pathologic processes including cytomegalovirus infection and Kaposi's sarcoma may be underrepresented in antemortem series.

Pulmonary Disease at Autopsy in Patients With the Acquired Immunodeficiency Syndrome

PubMed Central

Wallace, Jeanne M.; Hannah, James B.

1988-01-01

To characterize the postmortem pulmonary disease and analyze the effectiveness of antemortem diagnosis, we examined the clinical records and autopsy material from 54 patients who died of the acquired immunodeficiency syndrome. At autopsy, all patients had pulmonary disease. One or more specific diagnoses were made in 53, including opportunistic infection, nonopportunistic infection, and Kaposi's sarcoma. Multiple postmortem pulmonary diagnoses were established in 37. Respiratory failure was the most common cause of death. Of the 97 pulmonary disorders discovered at autopsy, only 31 were diagnosed before death. The frequency with which infections were diagnosed during life varied according to the organism, and was significantly higher for Pneumocystis carinii than for cytomegalovirus or bacterial agents. Pulmonary Kaposi's sarcoma was diagnosed in only 7% of patients with autopsy documentation. The yield of diagnostic procedures also varied according to the disease present. Sputum culture was relatively effective in detecting Cryptococcus neoformans and Mycobacterium avium-intracellulare, fiber-optic bronchoscopy was extremely useful for diagnosing P Carinii, and one or more diagnoses were provided in 4 of 7 patients who underwent thoracotomy, but significant disease including cytomegalovirus infection and pulmonary Kaposi's sarcoma was frequently missed. Although the spectrum of lung disease found at autopsy is similar to that observed during life, the frequency of some pathologic processes including cytomegalovirus infection and Kaposi's sarcoma may be underrepresented in antemortem series. PMID:3266812

Life-long shedding of Puumala hantavirus in wild bank voles (Myodes glareolus).

PubMed

Voutilainen, Liina; Sironen, Tarja; Tonteri, Elina; Bäck, Anne Tuiskunen; Razzauti, Maria; Karlsson, Malin; Wahlström, Maria; Niemimaa, Jukka; Henttonen, Heikki; Lundkvist, Åke

2015-06-01

The knowledge of viral shedding patterns and viraemia in the reservoir host species is a key factor in assessing the human risk of zoonotic viruses. The shedding of hantaviruses (family Bunyaviridae) by their host rodents has widely been studied experimentally, but rarely in natural settings. Here we present the dynamics of Puumala hantavirus (PUUV) shedding and viraemia in naturally infected wild bank voles (Myodes glareolus). In a monthly capture-mark-recapture study, we analysed 18 bank voles for the presence and relative quantity of PUUV RNA in the excreta and blood from 2 months before up to 8 months after seroconversion. The proportion of animals shedding PUUV RNA in saliva, urine and faeces peaked during the first month after seroconversion, but continued throughout the study period with only a slight decline. The quantity of shed PUUV in reverse transcription quantitative PCR (RT-qPCR) positive excreta was constant over time. In blood, PUUV RNA was present for up to 7 months but both the probability of viraemia and the virus load declined with time. Our findings contradict the current view of a decline in virus shedding after the acute phase and a short viraemic period in hantavirus infection - an assumption widely adopted in current epidemiological models. We suggest the life-long shedding as a means of hantaviruses to survive over host population bottlenecks, and to disperse in fragmented habitats where local host and/or virus populations face temporary extinctions. Our results indicate that the kinetics of pathogens in wild hosts may differ considerably from those observed in laboratory settings. © 2015 The Authors.

Down Syndrome with Complete Atrioventricular Septal Defect, Hypertrophic Cardiomyopathy, and Pulmonary Vein Stenosis.

PubMed

Mahadevaiah, Guruprasad; Gupta, Manoj; Ashwath, Ravi

2015-10-01

The prevalence of congenital heart disease in infants with Down syndrome is 40%, compared with 0.3% in children who have normal chromosomes. Atrioventricular and ventricular septal defects are often associated with chromosomal aberrations, such as in trisomy 21, whereas hypertrophic cardiomyopathy is chiefly thought to be secondary to specific gene mutations. We found only one reported case of congenital hypertrophic cardiomyopathy and atrioventricular septal defect in an infant with Down syndrome. Here, we report atrioventricular septal defect, hypertrophic cardiomyopathy, and pulmonary vein stenosis in a neonate with Down syndrome-an apparently unique combination. In addition, we discuss the relevant medical literature.

Reporting Hantavirus: A Study of Intercultural Environmental Journalism.

ERIC Educational Resources Information Center

Valenti, JoAnn M.

A study examined media coverage of hantavirus in three Southwestern regional newspapers, including interviews with journalists and sources involved in the coverage, and implications of the media's portrayal of Navajo culture. Content review of regional coverage--67 articles in three regional newspapers were reviewed in the first year of a new…

Country-wide seroprevalence studies on Crimean-Congo hemorrhagic fever and hantavirus infections in general population of Bulgaria.

PubMed

Christova, Iva; Panayotova, Elitsa; Trifonova, Iva; Taseva, Evgenia; Hristova, Teodora; Ivanova, Vladislava

2017-10-01

Crimean-Congo hemorrhagic fever (CCHF) and hantavirus infections are the two viral hemorrhagic fevers spread in Europe. To test actual circulation of CCHF virus (CCHFV) and hantaviruses in Bulgaria, we conducted country-wide seroepidemiological studies. Serum samples were collected prospectively from 1500 residents of all 28 districts in Bulgaria. CCHFV seroprevalence of 3.7% was revealed. Anamnesis for tick bites, contact with livestock, age over 40 years and residency in Haskovo district were found as risk factors. The highest CCHFV seroprevalence was observed in the known endemic districts in southeastern Bulgaria: Haskovo (28%) and Yambol (12%). Reactive samples were found in residents of 20 of the 28 districts in Bulgaria. In comparison with the previous studies, the data presented indicate that CCHFV increased substantially its circulation in the endemic regions and was introduced in many new areas. Hantavirus seroprevalence was based on results of the immunoblot and estimated as 3.1%. Surprisingly, contrary to all available data, Puumala virus seroprevalence rate was 2.3% versus 0.8% of Dobrava-Belgrade virus. Evidence for hantavirus IgG seropositivity was found in residents of 23 of the 28 districts in the country. The first hantavirus seroprevalence study in Bulgaria showed that Puumala virus is probably more wide-spread in the country than Dobrava-Belgrade virus. © 2017 Wiley Periodicals, Inc.

Neonatal pulmonary arterial hypertension and Noonan syndrome: two fatal cases with a specific RAF1 mutation.

PubMed

Hopper, Rachel K; Feinstein, Jeffrey A; Manning, Melanie A; Benitz, William; Hudgins, Louanne

2015-04-01

Mutations in RAF1 are associated with Noonan syndrome and hypertrophic cardiomyopathy. We present two infants with Noonan syndrome and an identical RAF1 mutation, p.Ser257Leu (c.770C>T), who developed severe pulmonary arterial hypertension (PAH) that proved to be fatal. The RAF1 gene encodes Raf-1 kinase, part of the Ras/mitogen-activated kinase (MAPK) signaling pathway, which has been linked to the development of PAH. This specific mutation has been associated with dephosphorylation of a critical serine residue and constitutive activation of the Raf-1 kinase. These two cases suggest that abnormal activation of the Ras/MAPK pathway may play a significant role in the development of pulmonary vascular disease in the subset of patients with Noonan syndrome and a specific RAF1 mutation. © 2015 Wiley Periodicals, Inc.

Pulmonary Hypertension Overview

MedlinePlus

... well as sleep apnea, are common causes of secondary pulmonary hypertension. Other causes include the following: Congestive heart failure Birth defects in the heart Chronic pulmonary thromboembolism (blood clots in the pulmonary arteries) Acquired immunodeficiency syndrome ( ...

Cutis laxa and fatal pulmonary hypertension: a newly recognized syndrome?

PubMed Central

Brunetti-Pierri, Nicola; Piccolo, Pasquale; Morava, Eva; Wevers, Ron A.; McGuirk, Megan; Johnson, Yvette R.; Urban, Zsolt; Dishop, Megan K.; Potocki, Lorraine

2015-01-01

Cutis laxa is a connective tissue disorder with distinctive lax, redundant, and inelastic skin. It is a genetically heterogenous disorder with autosomal dominant and recessive patterns of inheritance. We report a patient with cutis laxa supported by clinical, microscopic, and ultrastructural findings. Molecular analysis of fibulin-4 and -5, of the α2 subunit of the V-type H+ ATPase, and of the component of the oligomeric Golgi complex 7 (COG7) genes excluded the type I and type II autosomal recessive forms of cutis laxa, and congenital disorders of glycosylation associated with cutis laxa. Remarkably, our patient also presented severe and lethal pulmonary hypertension as a newborn. This case with cutis laxa, severe pulmonary hypertension, and no detectable mutations in fibulin-4 and -5 genes may represent a previously unrecognized syndrome. PMID:21285876

Leptospirosis pulmonary haemorrhage syndrome is associated with linear deposition of immunoglobulin and complement on the alveolar surface.

PubMed

Croda, J; Neto, A N D; Brasil, R A; Pagliari, C; Nicodemo, A C; Duarte, M I S

2010-06-01

Leptospirosis is a zoonotic infection associated with severe diseases such as leptospirosis pulmonary haemorrhage syndrome (LPHS). The cause of pulmonary haemorrhage is unclear. Understanding which mechanisms and processes are involved in LPHS will be important in treatment regimens under development for this life-threatening syndrome. In the present study, we evaluated 30 lung specimens from LPHS patients and seven controls using histology and immunohistochemistry (detection of IgM, IgG, IgA and C3) in order to describe the pathological features associated with this syndrome. Immunoglobulin deposits were detected on the alveolar surface in 18/30 LPHS patients. Three staining patterns were observed for the immunoglobulins and C3 in the lung tissues of LPHS patients: AS, delicate linear staining adjacent to the alveolar surface, which was indicative of a membrane covering the luminal surface of type I and II pneumocyte cells; S, heterogeneous staining which was sporadically distributed along the alveolar septum; and IA, weak, focal intra-alveolar granular staining. Human LPHS is associated with individual and unique histological patterns that differ from those of other causes of pulmonary haemorrhage. In the present study, it was found that the linear deposition of immunoglobulins (IgA, IgG and IgM) and complement on the alveolar surface may play a role in the pathogenesis of pulmonary haemorrhage in human leptospirosis.

Species Identity Supersedes the Dilution Effect Concerning Hantavirus Prevalence at Sites across Texas and México.

PubMed

Milholland, Matthew T; Castro-Arellano, Iván; Arellano, Elizabeth; Nava-García, Elizabeth; Rangel-Altamirano, Guadalupe; Gonzalez-Cozatl, Francisco X; Suzán, Gerardo; Schountz, Tony; González-Padrón, Shiara; Vigueras, Ana; Rubio, André V; Maikis, Troy J; Westrich, Bradford J; Martinez, Jose A; Esteve-Gassent, Maria D; Torres, Madison; Rodriguez-Ruiz, Erick R; Hahn, Dittmar; Lacher, Thomas E

2017-12-15

Recent models suggest a relationship exists between community diversity and pathogen prevalence, the proportion of individuals in a population that are infected by a pathogen, with most inferences tied to assemblage structure. Two contrasting outcomes of this relationship have been proposed: the "dilution effect" and the "amplification effect." Small mammal assemblage structure in disturbed habitats often differs from assemblages in sylvan environments, and hantavirus prevalence is often negatively correlated with habitats containing high species diversity via dilution effect dynamics. As species richness increases, prevalence of infection often is decreased. However, anthropogenic changes to sylvan landscapes have been shown to decrease species richness and/or increase phylogenetic similarities within assemblages. Between January 2011 and January 2016, we captured and tested 2406 individual small mammals for hantavirus antibodies at 20 sites across Texas and México and compared differences in hantavirus seroprevalence, species composition, and assemblage structure between sylvan and disturbed habitats. We found 313 small mammals positive for antibodies against hantaviruses, evincing an overall prevalence of 9.7% across all sites. In total, 40 species of small mammals were identified comprising 2 taxonomic orders (Rodentia and Eulipotyphla). By sampling both habitat types concurrently, we were able to make real-world inferences into the efficacy of dilution effect theory in terms of hantavirus ecology. Our hypothesis predicting greater species richness higher in sylvan habitats compared to disturbed areas was not supported, suggesting the characteristics of assemblage structure do not adhere to current conceptions of species richness negatively influencing prevalence via a dilution effect.

Human Puumala and Dobrava Hantavirus Infections in the Black Sea Region of Turkey: A Cross-Sectional Study

PubMed Central

Kalaycioglu, Handan; Uyar, Yavuz; Sevindi, Demet Furkan; Turkyilmaz, Bedia; Çakir, Vedat; Cindemir, Cengiz; Unal, Belgin; Yağçi-Çağlayik, Dilek; Korukluoglu, Gulay; Ertek, Mustafa; Heyman, Paul; Lundkvist, Åke

2013-01-01

Abstract This study was carried out to better understand the epidemiology of hantaviruses in a province of Turkey (Giresun) where human hantavirus disease has recently been detected. In this cross-sectional study, a total of 626 blood samples from healthy people aged 15 and 84 years old were collected both in urban and rural areas in 2009. The sera were tested by enzyme-linked immunosorbent assay (ELISA), immunoblotting assay, and the focus reduction neutralization test (FRNT). We screened the samples by an ELISA and found that 65/626 samples reacted positively for the presence of hantavirus-reactive immunoglobulin G (IgG). Twenty of the 65 ELISA-positive samples could be confirmed by an immunobloting assay, and the overall seroprevalence was thereby calculated to 3.2% (20/626). The seroprevalence of the people living in wood areas or adobe houses 9/17 (52.9%) was significantly higher than among people living in concrete houses 10/47 (21.3%) (p=0.014). Finally, 3 of the 20 immunoblot-positive sera were confirmed as specific for the Puumala hantavirus serotype by FRNT, 1 serum was confirmed as Dobrava virus-specific, whereas 1 serum was found to be equally reactive to Dobrava and Saaremaa viruses. We will now focus on further investigations of the ecology and epidemiology of hantaviruses in humans and their carrier animals in Turkey, studies that have already been started and will be further intensified. PMID:23289396

Prevalence and profile of congenital heart disease and pulmonary hypertension in Down syndrome in a pediatric cardiology service

PubMed Central

Mourato, Felipe Alves; Villachan, Lúcia Roberta R.; Mattos, Sandra da Silva

2014-01-01

OBJECTIVE: To determine the frequence and profile of congenital heart defects in Down syndrome patients referred to a pediatric cardiologic center, considering the age of referral, gender, type of heart disease diagnosed by transthoracic echocardiography and its association with pulmonary hypertension at the initial diagnosis. METHODS: Cross-sectional study with retrospective data collection of 138 patients with Down syndrome from a total of 17,873 records. Descriptive analysis of the data was performed, using Epi-Info version 7. RESULTS: Among the 138 patients with Down syndrome, females prevailed (56.1%) and 112 (81.2%) were diagnosed with congenital heart disease. The most common lesion was ostium secundum atrial septal defect, present in 51.8%, followed by atrioventricular septal defect, in 46.4%. Ventricular septal defects were present in 27.7%, while tetralogy of Fallot represented 6.3% of the cases. Other cardiac malformations corresponded to 12.5%. Pulmonary hypertension was associated with 37.5% of the heart diseases. Only 35.5% of the patients were referred before six months of age. CONCLUSIONS: The low percentage of referral until six months of age highlights the need for a better tracking of patients with Down syndrome in the context of congenital heart disease, due to the high frequency and progression of pulmonary hypertension. PMID:25119745

Pulmonary Vasculitis and a Horseshoe Kidney in Noonan Syndrome.

PubMed

Puvabanditsin, Surasak; Abellar, Rosanna; Madubuko, Adaora; Mehta, Rajeev; Walzer, Lauren

2018-01-01

We report a term male neonate with congenital myeloproliferative disorder, thrombocytopenia, a horseshoe kidney, feeding difficulty secondary to dysphagia/foregut dysmotility, and respiratory failure. Prenatal molecular genetic analysis revealed a fetus carrying c.184T>G (p.Tyr62Asp) pathogenic variant in PTPN11 . The infant eventually succumbed to respiratory failure. Bacterial and viral cultures/studies were all no growth/negative. Pulmonary capillaritis and vasculitis were noted at autopsy. This report presents a new case of Noonan syndrome with unusual associated disorders and a review of the literature.

Pulmonary Vasculitis and a Horseshoe Kidney in Noonan Syndrome

PubMed Central

Abellar, Rosanna; Madubuko, Adaora; Mehta, Rajeev

2018-01-01

We report a term male neonate with congenital myeloproliferative disorder, thrombocytopenia, a horseshoe kidney, feeding difficulty secondary to dysphagia/foregut dysmotility, and respiratory failure. Prenatal molecular genetic analysis revealed a fetus carrying c.184T>G (p.Tyr62Asp) pathogenic variant in PTPN11. The infant eventually succumbed to respiratory failure. Bacterial and viral cultures/studies were all no growth/negative. Pulmonary capillaritis and vasculitis were noted at autopsy. This report presents a new case of Noonan syndrome with unusual associated disorders and a review of the literature. PMID:29670795

First Molecular Evidence for Puumala Hantavirus in Poland

PubMed Central

Sheikh Ali, Hanan; Drewes, Stephan; Sadowska, Edyta T.; Mikowska, Magdalena; Groschup, Martin H.; Heckel, Gerald; Koteja, Pawel; Ulrich, Rainer G.

2014-01-01

Puumala virus (PUUV) causes mild to moderate cases of haemorrhagic fever with renal syndrome (HFRS), and is responsible for the majority of hantavirus infections of humans in Fennoscandia, Central and Western Europe. Although there are relatively many PUUV sequences available from different European countries, little is known about the presence of this virus in Poland. During population studies in 2009 a total of 45 bank voles were trapped at three sites in north-eastern Poland, namely islands on Dejguny and Dobskie Lakes and in a forest near Mikołajki. S and M segment-specific RT-PCR assays detected PUUV RNA in three animals from the Mikołajki site. The obtained partial S and M segment sequences demonstrated the highest similarity to the corresponding segments of a PUUV strain from Latvia. Analysis of chest cavity fluid samples by IgG ELISA using a yeast-expressed PUUV nucleocapsid protein resulted in the detection of two seropositive samples, both being also RT-PCR positive. Interestingly, at the trapping site in Mikołajki PUUV-positive bank voles belong to the Carpathian and Eastern genetic lineages within this species. In conclusion, we herein present the first molecular evidence for PUUV in the rodent reservoir from Poland. PMID:24452006

Simultaneous transcatheter closure of intralobar pulmonary sequestration and patent ductus arteriosus in a patient with infantile Scimitar syndrome.

PubMed

Aslan, Eyüp; Tanıdır, İbrahim Cansaran; Saygı, Murat; Onan, Sertaç Hanedan; Güzeltaş, Alper

2015-03-01

Scimitar syndrome is a rare disease associated with a right lung sequestration vascularised by arteries arising from the abdominal aorta and abnormal venous drainage into the inferior vena cava. The infantile form is generally presented with severe heart failure, pulmonary hypertension and respiratory distress. It may be associated with various intracardiac defects, including atrial septal defects, ventricular septal defects, patent ductus arteriosus or more complicated structural congenital heart defects. Here, we present a 2-month-old girl with Scimitar syndrome whose pulmonary arterial pressure decreased after transcatheter patent ductus arteriosus closure and embolization of the anomalous systemic arterial supply.

Immunohistochemical detection of IgM and IgG in lung tissue of dogs with leptospiral pulmonary haemorrhage syndrome (LPHS)

USDA-ARS?s Scientific Manuscript database

Leptospiral pulmonary haemorrhage syndrome (LPHS) is a severe form of leptospirosis. Pathogenic mechanisms are poorly understood. Lung tissues from 26 dogs with LPHS, 5 dogs with pulmonary haemorrhage due to other causes and 6 healthy lungs were labelled for IgG, IgM and leptospiral antigens. Three ...

Effects on Pulmonary Vascular Mechanics of Two Different Lung-Protective Ventilation Strategies in an Experimental Model of Acute Respiratory Distress Syndrome.

PubMed

Santos, Arnoldo; Gomez-Peñalver, Eva; Monge-Garcia, M Ignacio; Retamal, Jaime; Borges, João Batista; Tusman, Gerardo; Hedenstierna, Goran; Larsson, Anders; Suarez-Sipmann, Fernando

2017-11-01

To compare the effects of two lung-protective ventilation strategies on pulmonary vascular mechanics in early acute respiratory distress syndrome. Experimental study. University animal research laboratory. Twelve pigs (30.8 ± 2.5 kg). Acute respiratory distress syndrome was induced by repeated lung lavages and injurious mechanical ventilation. Thereafter, animals were randomized to 4 hours ventilation according to the Acute Respiratory Distress Syndrome Network protocol or to an open lung approach strategy. Pressure and flow sensors placed at the pulmonary artery trunk allowed continuous assessment of pulmonary artery resistance, effective elastance, compliance, and reflected pressure waves. Respiratory mechanics and gas exchange data were collected. Acute respiratory distress syndrome led to pulmonary vascular mechanics deterioration. Four hours after randomization, pulmonary vascular mechanics was similar in Acute Respiratory Distress Syndrome Network and open lung approach: resistance (578 ± 252 vs 626 ± 153 dyn.s/cm; p = 0.714), effective elastance, (0.63 ± 0.22 vs 0.58 ± 0.17 mm Hg/mL; p = 0.710), compliance (1.19 ± 0.8 vs 1.50 ± 0.27 mL/mm Hg; p = 0.437), and reflection index (0.36 ± 0.04 vs 0.34 ± 0.09; p = 0.680). Open lung approach as compared to Acute Respiratory Distress Syndrome Network was associated with improved dynamic respiratory compliance (17.3 ± 2.6 vs 10.5 ± 1.3 mL/cm H2O; p < 0.001), driving pressure (9.6 ± 1.3 vs 19.3 ± 2.7 cm H2O; p < 0.001), and venous admixture (0.05 ± 0.01 vs 0.22 ± 0.03, p < 0.001) and lower mean pulmonary artery pressure (26 ± 3 vs 34 ± 7 mm Hg; p = 0.045) despite of using a higher positive end-expiratory pressure (17.4 ± 0.7 vs 9.5 ± 2.4 cm H2O; p < 0.001). Cardiac index, however, was lower in open lung approach (1.42 ± 0.16 vs 2.27 ± 0.48 L/min; p = 0.005). In this experimental model, Acute

High-Dose Intravenous Methylprednisolone for Hantavirus Cardiopulmonary Syndrome in Chile: A Double-Blind, Randomized Controlled Clinical Trial

PubMed Central

Vial, Pablo A.; Valdivieso, Francisca; Ferres, Marcela; Riquelme, Raul; Rioseco, M. Luisa; Calvo, Mario; Castillo, Constanza; Díaz, Ricardo; Scholz, Luis; Cuiza, Analia; Belmar, Edith; Hernandez, Carla; Martinez, Jessica; Lee, Sang-Joon; Mertz, Gregory J.; Abarca, Juan; Tomicic, Vinko; Aracena, M. Eugenia; Rehbein, Ana Maria; Velásquez, Soledad; Lavin, Victoria; Garrido, Felipe; Godoy, Paula; Martinez, Constanza; Chamorro, Juan Carlos; Contreras, Jorge; Hernandez, Jury; Pino, Marcelo; Villegas, Paola; Zapata, Viviana; León, Marisol; Vega, Ivonne; Otarola, Irisol; Ortega, Carlos; Daube, Elizabeth; Huecha, Doris; Neira, Alda; Ruiz, Ines; Nuñez, M. Antonieta; Monsalve, Luz; Chabouty, Henriette; Riquelme, Lorena; Palma, Samia; Bustos, Raul; Miranda, Ruben; Mardones, Jovita; Hernandez, Nora; Betancur, Yasna; Sanhueza, Ligia; Inostroza, Jaime; Donoso, Solange; Navarrete, Maritza; Acuña, Lily; Manriquez, Paulina; Castillo, Fabiola; Unzueta, Paola; Aguilera, Teresa; Osorio, Carola; Yobanolo, Veronica; Mardones, Jorge; Aranda, Sandra; Carvajal, Soledad; Sandoval, Moisés; Daza, Soraya; Vargas, Felipe; Diaz, Violeta; Riquelme, Mauricio; Muñoz, Miriam; Carriel, Andrea; Lanino, Paola; Hernandez, Susana; Schumacher, Patricia; Yañez, Lia; Marco, Claudia; Ehrenfeld, Mildred; Delgado, Iris; Rios, Susana; Vial, Cecilia; Bedrick, Edward

2013-01-01

Background. Andes virus (ANDV)–related hantavirus cardiopulmonary syndrome (HCPS) has a 35% case fatality rate in Chile and no specific treatment. In an immunomodulatory approach, we evaluated the efficacy of intravenous methylprednisolone for HCPS treatment, through a parallel-group, placebo-controlled clinical trial. Methods. Patients aged >2 years, with confirmed or suspected HCPS in cardiopulmonary stage, admitted to any of 13 study sites in Chile, were randomized by study center in blocks of 4 with a 1:1 allocation and assigned through sequentially numbered envelopes to receive placebo or methylprednisolone 16 mg/kg/day (≤1000 mg) for 3 days. All personnel remained blinded except the local pharmacist. Infection was confirmed by immunoglobulin M antibodies or ANDV RNA in blood. The composite primary endpoint was death, partial pressure of arterial oxygen/fraction of inspired oxygen ratio ≤55, cardiac index ≤2.2, or ventricular tachycardia or fibrillation within 28 days. Safety endpoints included the number of serious adverse events (SAEs) and quantification of viral RNA in blood. Analysis was by intention to treat. Results. Infection was confirmed in 60 of 66 (91%) enrollees. Fifteen of 30 placebo-treated patients and 11 of 30 methylprednisolone-treated patients progressed to the primary endpoint (P = .43). We observed no significant difference in mortality between treatment groups (P = .41). There was a trend toward more severe disease in placebo recipients at entry. More subjects in the placebo group experienced SAEs (P = .02). There were no SAEs clearly related to methylprednisolone administration, and methylprednisolone did not increase viral load. Conclusions. Although methylprednisolone appears to be safe, it did not provide significant clinical benefit to patients. Our results do not support the use of methylprednisolone for HCPS. Clinical Trials Registration. NCT00128180. PMID:23784924

High-dose intravenous methylprednisolone for hantavirus cardiopulmonary syndrome in Chile: a double-blind, randomized controlled clinical trial.

PubMed

Vial, Pablo A; Valdivieso, Francisca; Ferres, Marcela; Riquelme, Raul; Rioseco, M Luisa; Calvo, Mario; Castillo, Constanza; Díaz, Ricardo; Scholz, Luis; Cuiza, Analia; Belmar, Edith; Hernandez, Carla; Martinez, Jessica; Lee, Sang-Joon; Mertz, Gregory J

2013-10-01

Andes virus (ANDV)-related hantavirus cardiopulmonary syndrome (HCPS) has a 35% case fatality rate in Chile and no specific treatment. In an immunomodulatory approach, we evaluated the efficacy of intravenous methylprednisolone for HCPS treatment, through a parallel-group, placebo-controlled clinical trial. Patients aged >2 years, with confirmed or suspected HCPS in cardiopulmonary stage, admitted to any of 13 study sites in Chile, were randomized by study center in blocks of 4 with a 1:1 allocation and assigned through sequentially numbered envelopes to receive placebo or methylprednisolone 16 mg/kg/day (≤1000 mg) for 3 days. All personnel remained blinded except the local pharmacist. Infection was confirmed by immunoglobulin M antibodies or ANDV RNA in blood. The composite primary endpoint was death, partial pressure of arterial oxygen/fraction of inspired oxygen ratio ≤55, cardiac index ≤2.2, or ventricular tachycardia or fibrillation within 28 days. Safety endpoints included the number of serious adverse events (SAEs) and quantification of viral RNA in blood. Analysis was by intention to treat. Infection was confirmed in 60 of 66 (91%) enrollees. Fifteen of 30 placebo-treated patients and 11 of 30 methylprednisolone-treated patients progressed to the primary endpoint (P = .43). We observed no significant difference in mortality between treatment groups (P = .41). There was a trend toward more severe disease in placebo recipients at entry. More subjects in the placebo group experienced SAEs (P = .02). There were no SAEs clearly related to methylprednisolone administration, and methylprednisolone did not increase viral load. Although methylprednisolone appears to be safe, it did not provide significant clinical benefit to patients. Our results do not support the use of methylprednisolone for HCPS. NCT00128180.

Rickettsia bellii, Rickettsia amblyommii, and Laguna Negra hantavirus in an Indian reserve in the Brazilian Amazon.

PubMed

de Barros Lopes, Lívia; Guterres, Alexandro; Rozental, Tatiana; Carvalho de Oliveira, Renata; Mares-Guia, Maria Angélica; Fernandes, Jorlan; Figueredo, José Ferreira; Anschau, Inês; de Jesus, Sebastião; V Almeida, Ana Beatriz M; Cristina da Silva, Valéria; Gomes de Melo Via, Alba Valéria; Bonvicino, Cibele Rodrigues; D'Andrea, Paulo Sérgio; Barreira, Jairo Dias; Sampaio de Lemos, Elba Regina

2014-04-17

The purpose of this study was to identify the presence of rickettsia and hantavirus in wild rodents and arthropods in response to an outbreak of acute unidentified febrile illness among Indians in the Halataikwa Indian Reserve, northwest of the Mato Grosso state, in the Brazilian Amazon. Where previously surveillance data showed serologic evidence of rickettsia and hantavirus human infection. The arthropods were collected from the healthy Indian population and by flagging vegetation in grassland or woodland along the peridomestic environment of the Indian reserve. Wild rodents were live-trapped in an area bordering the reserve limits, due the impossibility of capturing wild animals in the Indian reserve. The wild rodents were identified based on external and cranial morphology and karyotype. DNA was extracted from spleen or liver samples of rodents and from invertebrate (tick and louse) pools, and the molecular characterization of the rickettsia was through PCR and DNA sequencing of fragments of two rickettsial genes (gltA and ompA). In relation to hantavirus, rodent serum samples were serologically screened by IgG ELISA using the Araraquara-N antigen and total RNA was extracted from lung samples of IgG-positive rodents. The amplification of the complete S segment was performed. A total of 153 wild rodents, 121 louse, and 36 tick specimens were collected in 2010. Laguna Negra hantavirus was identified in Calomys callidus rodents and Rickettsia bellii, Rickettsia amblyommii were identified in Amblyomma cajennense ticks. Zoonotic diseases such as HCPS and spotted fever rickettsiosis are a public health threat and should be considered in outbreaks and acute febrile illnesses among Indian populations. The presence of the genome of rickettsias and hantavirus in animals in this Indian reserve reinforces the need to include these infectious agents in outbreak investigations of febrile cases in Indian populations.

Primary Pulmonary Ewing's Sarcoma: Rare Cause of Superior Vena Cava Syndrome in Children.

PubMed

Mehra, Shibani; Atwal, Swapndeep Singh; Garga, Umesh Chandra

2014-08-01

Ewing's sarcoma is a common malignant bone tumour presenting in children and young adults. Rarely extra- skeletal soft tissues and visceral organs can also be the site of origin of Ewing's sarcoma. Primary pulmonary Ewing's sarcoma is an extremely rare malignancy which occurs in the paediatric population. We report an unusual case of primary pulmonary Ewing's sarcoma in a nine year old girl who presented with features of superior vena cava syndrome in the emergency department. The diagnosis was confirmed pathologically both by light microscopy and immunohistochemistry. The patient was put on chemotherapy and surgery was planned but the patient expired within three days of starting chemotherapy.

Experimental Evidence for Reduced Rodent Diversity Causing Increased Hantavirus Prevalence

PubMed Central

Suzán, Gerardo; Marcé, Erika; Giermakowski, J. Tomasz; Mills, James N.; Ceballos, Gerardo; Ostfeld, Richard S.; Armién, Blas; Pascale, Juan M.; Yates, Terry L.

2009-01-01

Emerging and re-emerging infectious diseases have become a major global environmental problem with important public health, economic, and political consequences. The etiologic agents of most emerging infectious diseases are zoonotic, and anthropogenic environmental changes that affect wildlife communities are increasingly implicated in disease emergence and spread. Although increased disease incidence has been correlated with biodiversity loss for several zoonoses, experimental tests in these systems are lacking. We manipulated small-mammal biodiversity by removing non-reservoir species in replicated field plots in Panama, where zoonotic hantaviruses are endemic. Both infection prevalence of hantaviruses in wild reservoir (rodent) populations and reservoir population density increased where small-mammal species diversity was reduced. Regardless of other variables that affect the prevalence of directly transmitted infections in natural communities, high biodiversity is important in reducing transmission of zoonotic pathogens among wildlife hosts. Our results have wide applications in both conservation biology and infectious disease management. PMID:19421313

Nephrotic syndrome presenting as deep vein thrombosis or pulmonary embolism.

PubMed

Ambler, Bill; Irvine, Sharon; Selvarajah, Vik; Isles, Chris

2008-04-01

A patient presenting with a swollen left leg and pleuritic chest pain was shown to have deep vein thrombosis (DVT) by Doppler studies. He was anticoagulated but required two further admissions with swelling of both legs before a diagnosis of nephrotic syndrome was considered and confirmed. Renal biopsy showed that this was caused by membranous nephropathy. Two audits were subsequently conducted. The first was of diagnostic discharge codes for nephrotic syndrome and venous thromboembolism in south west Scotland (population 147,000) from 1997 to 2006. A diagnosis of nephrotic syndrome was confirmed in 32 patients, four (12.5%) of whom (including the index case) had presented with DVT (two) or pulmonary embolus (PE) (two). A second audit of 98 consecutive patients with Doppler-positive lower limb DVT presenting to A&E in Dumfries from July 2005 to July 2006 showed that the urine had been tested for protein in one case only. Although nephrotic syndrome remains an uncommon cause of DVT or PE, it is complicated by venous thromboembolism sufficiently frequently for the diagnosis to be considered in all patients with DVT or PE, for whom the take-home message should simply be-Don't forget to dip the urine or ignore a low serum albumin.

Estimating hantavirus risk in southern Argentina: a GIS-based approach combining human cases and host distribution.

PubMed

Andreo, Veronica; Neteler, Markus; Rocchini, Duccio; Provensal, Cecilia; Levis, Silvana; Porcasi, Ximena; Rizzoli, Annapaola; Lanfri, Mario; Scavuzzo, Marcelo; Pini, Noemi; Enria, Delia; Polop, Jaime

2014-01-14

We use a Species Distribution Modeling (SDM) approach along with Geographic Information Systems (GIS) techniques to examine the potential distribution of hantavirus pulmonary syndrome (HPS) caused by Andes virus (ANDV) in southern Argentina and, more precisely, define and estimate the area with the highest infection probability for humans, through the combination with the distribution map for the competent rodent host (Oligoryzomys longicaudatus). Sites with confirmed cases of HPS in the period 1995-2009 were mostly concentrated in a narrow strip (~90 km × 900 km) along the Andes range from northern Neuquén to central Chubut province. This area is characterized by high mean annual precipitation (~1,000 mm on average), but dry summers (less than 100 mm), very low percentages of bare soil (~10% on average) and low temperatures in the coldest month (minimum average temperature -1.5 °C), as compared to the HPS-free areas, features that coincide with sub-Antarctic forests and shrublands (especially those dominated by the invasive plant Rosa rubiginosa), where rodent host abundances and ANDV prevalences are known to be the highest. Through the combination of predictive distribution maps of the reservoir host and disease cases, we found that the area with the highest probability for HPS to occur overlaps only 28% with the most suitable habitat for O. longicaudatus. With this approach, we made a step forward in the understanding of the risk factors that need to be considered in the forecasting and mapping of risk at the regional/national scale. We propose the implementation and use of thematic maps, such as the one built here, as a basic tool allowing public health authorities to focus surveillance efforts and normally scarce resources for prevention and control actions in vast areas like southern Argentina.

Estimating Hantavirus Risk in Southern Argentina: A GIS-Based Approach Combining Human Cases and Host Distribution

PubMed Central

Andreo, Veronica; Neteler, Markus; Rocchini, Duccio; Provensal, Cecilia; Levis, Silvana; Porcasi, Ximena; Rizzoli, Annapaola; Lanfri, Mario; Scavuzzo, Marcelo; Pini, Noemi; Enria, Delia; Polop, Jaime

2014-01-01

We use a Species Distribution Modeling (SDM) approach along with Geographic Information Systems (GIS) techniques to examine the potential distribution of hantavirus pulmonary syndrome (HPS) caused by Andes virus (ANDV) in southern Argentina and, more precisely, define and estimate the area with the highest infection probability for humans, through the combination with the distribution map for the competent rodent host (Oligoryzomys longicaudatus). Sites with confirmed cases of HPS in the period 1995–2009 were mostly concentrated in a narrow strip (~90 km × 900 km) along the Andes range from northern Neuquén to central Chubut province. This area is characterized by high mean annual precipitation (~1,000 mm on average), but dry summers (less than 100 mm), very low percentages of bare soil (~10% on average) and low temperatures in the coldest month (minimum average temperature −1.5 °C), as compared to the HPS-free areas, features that coincide with sub-Antarctic forests and shrublands (especially those dominated by the invasive plant Rosa rubiginosa), where rodent host abundances and ANDV prevalences are known to be the highest. Through the combination of predictive distribution maps of the reservoir host and disease cases, we found that the area with the highest probability for HPS to occur overlaps only 28% with the most suitable habitat for O. longicaudatus. With this approach, we made a step forward in the understanding of the risk factors that need to be considered in the forecasting and mapping of risk at the regional/national scale. We propose the implementation and use of thematic maps, such as the one built here, as a basic tool allowing public health authorities to focus surveillance efforts and normally scarce resources for prevention and control actions in vast areas like southern Argentina. PMID:24424500

Testing and Validation of High Density Resequencing Microarray for Broad Range Biothreat Agents Detection

DTIC Science & Technology

2009-08-11

Competing Interests: One of the contributing authors : Clark Tibbetts, is the Executive Vice President and Chief Technology Officer of Tessarae, LLC...Detection 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR (S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7...N/A 1021 ng No detection Sin nombre Bunyaviridae III 1021 ng Pulmonary syndrome hantavirus strain Convict Creek 107 1CCHFV = Crimean-Congo hemorrhagic

Vascular Ehlers-Danlos Syndrome With a Novel Missense COL3A1 Mutation Present With Pulmonary Complications and Iliac Arterial Dissection.

PubMed

Gu, Guangchao; Yang, Hang; Cui, Lijia; Fu, Yuanyuan; Li, Fangda; Zhou, Zhou; Zheng, Yuehong

2018-02-01

Vascular Ehlers-Danlos syndrome (vEDS) is a life-threatening connective tissue disorder due to its high tendency of arterial and organ rupture. Pulmonary complications in vEDS are rare. We present a young male patient with vEDS who developed severe pulmonary complications and severe rupture of the iliac artery at different stages of his life. Vascular Ehlers-Danlos syndrome was diagnosed based on clinical manifestations and confirmed by the identification of COL3A1 gene mutation. Due to high bleeding tendency and weak cardiopulmonary capacity, conservative treatment was taken for him. To our knowledge, this is the first report of vEDS case in which the patient developed both pulmonary complications and dissection of large arteries. Our report emphasizes the importance of considering vEDS when an adolescent develops unexplained pulmonary cysts with fragility of lung tissues. Genetic counseling and close monitoring should be performed for earlier diagnosis and prevention of severe complications of large arteries. The typical presentations of vEDS were also discussed by means of a review of case reports on vEDS with pulmonary complications.

The Andes Virus Nucleocapsid Protein Directs Basal Endothelial Cell Permeability by Activating RhoA

PubMed Central

Gorbunova, Elena E.; Simons, Matthew J.; Gavrilovskaya, Irina N.

2016-01-01

ABSTRACT Andes virus (ANDV) predominantly infects microvascular endothelial cells (MECs) and nonlytically causes an acute pulmonary edema termed hantavirus pulmonary syndrome (HPS). In HPS patients, virtually every pulmonary MEC is infected, MECs are enlarged, and infection results in vascular leakage and highly lethal pulmonary edema. We observed that MECs infected with the ANDV hantavirus or expressing the ANDV nucleocapsid (N) protein showed increased size and permeability by activating the Rheb and RhoA GTPases. Expression of ANDV N in MECs increased cell size by preventing tuberous sclerosis complex (TSC) repression of Rheb-mTOR-pS6K. N selectively bound the TSC2 N terminus (1 to 1403) within a complex containing TSC2/TSC1/TBC1D7, and endogenous TSC2 reciprocally coprecipitated N protein from ANDV-infected MECs. TSCs normally restrict RhoA-induced MEC permeability, and we found that ANDV infection or N protein expression constitutively activated RhoA. This suggests that the ANDV N protein alone is sufficient to activate signaling pathways that control MEC size and permeability. Further, RhoA small interfering RNA, dominant-negative RhoA(N19), and the RhoA/Rho kinase inhibitors fasudil and Y27632 dramatically reduced the permeability of ANDV-infected MECs by 80 to 90%. Fasudil also reduced the bradykinin-directed permeability of ANDV and Hantaan virus-infected MECs to control levels. These findings demonstrate that ANDV activation of RhoA causes MEC permeability and reveal a potential edemagenic mechanism for ANDV to constitutively inhibit the basal barrier integrity of infected MECs. The central importance of RhoA activation in MEC permeability further suggests therapeutically targeting RhoA, TSCs, and Rac1 as potential means of resolving capillary leakage during hantavirus infections. PMID:27795403

Interstage evaluation of homograft-valved right ventricle to pulmonary artery conduits for palliation of hypoplastic left heart syndrome.

PubMed

Sandeep, Nefthi; Punn, Rajesh; Balasubramanian, Sowmya; Smith, Shea N; Reinhartz, Olaf; Zhang, Yulin; Wright, Gail E; Peng, Lynn F; Wise-Faberowski, Lisa; Hanley, Frank L; McElhinney, Doff B

2018-04-01

Palliation of hypoplastic left heart syndrome with a standard nonvalved right ventricle to pulmonary artery conduit results in an inefficient circulation in part due to diastolic regurgitation. A composite right ventricle pulmonary artery conduit with a homograft valve has a hypothetical advantage of reducing regurgitation, but may differ in the propensity for stenosis because of valve remodeling. This retrospective cohort study included 130 patients with hypoplastic left heart syndrome who underwent a modified stage 1 procedure with a right ventricle to pulmonary artery conduit from 2002 to 2015. A composite valved conduit (cryopreserved homograft valve anastomosed to a polytetrafluoroethylene tube) was placed in 100 patients (47 aortic, 32 pulmonary, 13 femoral/saphenous vein, 8 unknown), and a nonvalved conduit was used in 30 patients. Echocardiographic functional parameters were evaluated before and after stage 1 palliation and before the bidirectional Glenn procedure, and interstage interventions were assessed. On competing risk analysis, survival over time was better in the valved conduit group (P = .040), but this difference was no longer significant after adjustment for surgical era. There was no significant difference between groups in the cumulative incidence of bidirectional Glenn completion (P = .15). Patients with a valved conduit underwent more interventions for conduit obstruction in the interstage period, but this difference did not reach significance (P = .16). There were no differences between groups in echocardiographic parameters of right ventricle function at baseline or pre-Glenn. In this cohort of patients with hypoplastic left heart syndrome, inclusion of a valved right ventricle to pulmonary artery conduit was not associated with any difference in survival on adjusted analysis and did not confer an identifiable benefit on right ventricle function. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier

Dietary N,N-dimethylglycine supplementation improves nutrient digestibility and attenuates pulmonary hypertension syndrome in broilers.

PubMed

Kalmar, I D; Cools, A; Buyse, J; Roose, P; Janssens, G P J

2010-12-01

N,N-dimethylglycine (DMG) is an intermediary metabolite in cellular choline and betaine metabolism. The present trial aimed to evaluate the effect of dietary DMG on nutrient digestibility and development of pulmonary hypertension syndrome in broilers. A total of 64 14-day-old broiler hens (Ross-308) were raised until age 40 days under cold environmental temperature conditions (15 °C) and were fed a high energy feed in order to incite pulmonary hypertension. Birds were randomly assigned to two groups of which each group had eight replicate pens of four birds each. Test diets contained 0 or 167 mg Na-DMG (Taminizer(®) D; Taminco N.V., Ghent, Belgium)/kg feed. N,N-dimethylglycine supplementation resulted in a significant improvement in apparent faecal digestibility of crude protein and nitrogen-free extract. Further, fulminant ascites was numerically lowered by DMG and incidence of pulmonary hypertension decreased significantly from 44.8% in the control group to 14.6% in the DMG group. Finally, fasted plasma level of non-esterified fatty acids (NEFA) was twofold in the control group in relation to the DMG group. In conclusion, these data demonstrate beneficial effects of DMG on digestibility of non-fat fractions, on fat metabolism and on progression towards broiler ascites syndrome. © 2010 Blackwell Verlag GmbH.

Tula and Puumala hantavirus NSs ORFs are functional and the products inhibit activation of the interferon-beta promoter.

PubMed

Jääskeläinen, Kirsi M; Kaukinen, Pasi; Minskaya, Ekaterina S; Plyusnina, Angelina; Vapalahti, Olli; Elliott, Richard M; Weber, Friedemann; Vaheri, Antti; Plyusnin, Alexander

2007-10-01

The S RNA genome segment of hantaviruses carried by Arvicolinae and Sigmodontinae rodents encodes the nucleocapsid (N) protein and has an overlapping (+1) open reading frame (ORF) for a putative nonstructural protein (NSs). The aim of this study was to determine whether the ORF is functional. A protein corresponding to the predicted size of Tula virus (TULV) NSs was detected using coupled in vitro transcription and translation from a cloned S segment cDNA, and a protein corresponding to the predicted size of Puumala virus (PUUV) NSs was detected in infected cells by Western blotting with an anti-peptide serum. The activities of the interferon beta (IFN-beta) promoter, and nuclear factor kappa B (NF-kappaB)- and interferon regulatory factor-3 (IRF-3) responsive promoters, were inhibited in COS-7 cells transiently expressing TULV or PUUV NSs. Also IFN-beta mRNA levels in IFN-competent MRC5 cells either infected with TULV or transiently expressing NSs were decreased. These data demonstrate that Tula and Puumala hantaviruses have a functional NSs ORF. The findings may explain why the NSs ORF has been preserved in the genome of most hantaviruses during their long evolution and why hantavirus-infected cells secrete relatively low levels of IFNs. (c) 2007 Wiley-Liss, Inc.

Emerging Viruses in the Republic of Suriname: Retrospective and Prospective Study into Chikungunya Circulation and Suspicion of Human Hantavirus Infections, 2008-2012 and 2014.

PubMed

Goeijenbier, Marco; Aron, Georgina; Anfasa, Fatih; Lundkvist, Åke; Verner-Carlsson, Jenny; Reusken, Chantal B E M; Martina, Byron E E; van Gorp, Eric C M; Resida, Lesley

2015-10-01

Suriname is a country on the northeastern Atlantic coast of South America. It is unique in the sense that different ethnic cultures live together within the country, resulting in high levels of transport of both humans and products between the Asian, African, and European continents as well as the Caribbean. Travel is only one of the many factors present in Suriname contributing to the risk for the emergence or introduction of any infectious disease. Recently, circulation of both chikungunya virus (CHIKV) and hantavirus was reported in areas neighboring Suriname. Here we report a retrospective and prospective study into chikungunya and hantavirus circulation. A chikungunya and hantavirus retrospective serological study was conducted on samples submitted for dengue, leptospirosis, and/or influenza virus diagnostics between 2008 and 2012 to the Bureau of Public Health in Suriname. This was followed by a prospective CHIKV serological and molecular surveillance study until the detection of the first autochthonous CHIKV cases in Suriname in May and June of 2014. None of the tested samples showed the presence of CHIKV antibodies in the retrospective serological study. Prospective testing of CHIKV-suspected patients resulted in the detection of the first autochthonous CHIKV cases in Suriname in May, 2015. In one sample, we were able to isolate and sequence the virus. Retrospective testing for the presence of hantavirus antibodies showed a relative high response in both pan-hantavirus enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA). However, neutralization tests did not yield any evidence for infection with either Seoul or Andes hantavirus. Here we report the presence of CHIKV in the republic of Suriname and the first serological indication of hantavirus infections in symptomatic patients.

Hantavirus infection--southwestern United States: interim recommendations for risk reduction. Centers for Disease Control and Prevention.

PubMed

Childs, J E; Kaufmann, A F; Peters, C J; Ehrenberg, R L

1993-07-30

This report provides interim recommendations for prevention and control of hantavirus infections associated with rodents in the southwestern United States. It is based on principles of rodent and infection control and contains specific recommendations for reducing rodent shelter and food sources in and around the home, recommendations for eliminating rodents inside the home and preventing them from entering the home, precautions for preventing hantavirus infection while rodent-contaminated areas are being cleaned up, prevention measures for persons who have occupational exposure to wild rodents, and precautions for campers and hikers.

Recurrent Pulmonary Aneurysms: Hughes-Stovin Syndrome on the Spectrum of Behçet Disease.

PubMed

Bennji, Sami M; du Preez, Leonard; Griffith-Richards, Stephanie; Smit, Derrick P; Rigby, Jonathan; Koegelenberg, Coenraad F N; Irusen, Elvis M; Allwood, Brian W

2017-11-01

In this report, we describe a male patient who presented with recurrent life-threatening hemoptysis due to the sequential formation of multiple pulmonary aneurysms. Both pulmonary artery coil embolization and right lower lobectomy were performed, with limited success. The patient experienced extensive bilateral femoral DVT extending into the inferior vena cava, with massive hemoptysis, fulfilling the diagnosis of Hughes-Stovin syndrome. A final diagnosis of Behçet disease was made following extensive investigation, and the patient responded well to prednisone 20 mg orally and azathioprine 100 mg orally. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Pulmonary vasculature and critical asthma syndromes: a comprehensive review.

PubMed

Avdalovic, Mark

2015-02-01

One of the important factors and consequences in persistent asthma is the change in the vasculature of the airways and lung parenchyma. These changes could contribute to worsening asthma control and predispose asthmatics to critical asthma syndromes. For many years, the contribution of vasculature to severe asthma was limited to discussion of small and medium vessel vasculitis commonly referred to as Churg-Strauss syndrome. This comprehensive review will explore the known mechanisms that are associated with remodeling of the vasculature in a variety of critical asthma presentations. Inflammation of pulmonary and bronchial small blood vessels may contribute significantly but silently to asthma pathobiology. Inflammation in the vasculature of the lung parenchyma can decrease lung capacity while inflammation in airway vasculature can decrease airflow. This review will provide a modern perspective on Churg-Strauss syndromes with a focus on phenotyping, mechanism, and ultimately modern therapeutic approaches. Vascular remodeling and airway remodeling are not mutually exclusive concepts in understanding the progression of asthma and frequency of acute exacerbations. Furthermore, the contribution of vascular leak, particularly in the parenchymal vasculature, has become an increasingly recognized component of certain presentations of poorly controlled, severe persistent asthmatic and during exacerbations. We highlight how these mechanisms can contribute to some the severe presentations of influenza infection in patients with a history of asthma. The ultimate aim of this review is to summarize the current literature concerning vasculitis and the contribution of airway and parenchymal vascular remodeling to presentation of persistent asthma and its consequences during acute exacerbations and critical asthma syndromes.

Syndrome complex of bone marrow failure and pulmonary fibrosis predicts germline defects in telomerase

PubMed Central

Parry, Erin M.; Alder, Jonathan K.; Qi, Xiaodong; Chen, Julian J.-L.

2011-01-01

Mutations in the essential telomerase components hTERT and hTR cause dyskeratosis congenita, a bone marrow failure syndrome characterized by mucocutaneous features. Some (∼ 3%) sporadic aplastic anemia (AA) and idiopathic pulmonary fibrosis cases also carry mutations in hTERT and hTR. Even though it can affect clinical outcome, because the mutation frequency is rare, genetic testing is not standard. We examined whether the cooccurrence of bone marrow failure and pulmonary fibrosis in the same individual or family enriches for the presence of a telomerase mutation. Ten consecutive individuals with a total of 36 family members who fulfilled these criteria carried a germline mutant telomerase gene (100%). The mean age of onset for individuals with AA was significantly younger than that for those with pulmonary fibrosis (14 vs 51; P < .0001). Families displayed autosomal dominant inheritance and there was an evolving pattern of genetic anticipation, with the older generation primarily affected by pulmonary fibrosis and successive generations by bone marrow failure. The cooccurrence of AA and pulmonary fibrosis in a single patient or family is highly predictive for the presence of a germline telomerase defect. This diagnosis affects the choice of bone marrow transplantation preparative regimen and can prevent morbidity. PMID:21436073

Immunogenetic Factors Affecting Susceptibility of Humans and Rodents to Hantaviruses and the Clinical Course of Hantaviral Disease in Humans

PubMed Central

Charbonnel, Nathalie; Pagès, Marie; Sironen, Tarja; Henttonen, Heikki; Vapalahti, Olli; Mustonen, Jukka; Vaheri, Antti

2014-01-01

We reviewed the associations of immunity-related genes with susceptibility of humans and rodents to hantaviruses, and with severity of hantaviral diseases in humans. Several class I and class II HLA haplotypes were linked with severe or benign hantavirus infections, and these haplotypes varied among localities and hantaviruses. The polymorphism of other immunity-related genes including the C4A gene and a high-producing genotype of TNF gene associated with severe PUUV infection. Additional genes that may contribute to disease or to PUUV infection severity include non-carriage of the interleukin-1 receptor antagonist (IL-1RA) allele 2 and IL-1β (-511) allele 2, polymorphisms of plasminogen activator inhibitor (PAI-1) and platelet GP1a. In addition, immunogenetic studies have been conducted to identify mechanisms that could be linked with the persistence/clearance of hantaviruses in reservoirs. Persistence was associated during experimental infections with an upregulation of anti-inflammatory responses. Using natural rodent population samples, polymorphisms and/or expression levels of several genes have been analyzed. These genes were selected based on the literature of rodent or human/hantavirus interactions (some Mhc class II genes, Tnf promoter, and genes encoding the proteins TLR4, TLR7, Mx2 and β3 integrin). The comparison of genetic differentiation estimated between bank vole populations sampled over Europe, at neutral and candidate genes, has allowed to evidence signatures of selection for Tnf, Mx2 and the Drb Mhc class II genes. Altogether, these results corroborated the hypothesis of an evolution of tolerance strategies in rodents. We finally discuss the importance of these results from the medical and epidemiological perspectives. PMID:24859344

Goodpasture syndrome

MedlinePlus

... pulmonary hemorrhage; Pulmonary renal syndrome; Glomerulonephritis - pulmonary hemorrhage Images Kidney blood supply References Appel GB, Radhakrishnan J, D'Agati V. Secondary glomerular disease. In: Skorecki ...

Characterization of Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome: A Qualitative Analysis.

PubMed

Rodrigue, Claudie; Beauchesne, Marie-France; Mallette, Valérie; Lemière, Catherine; Larivée, Pierre; Blais, Lucie

2017-06-01

Approximately 15-20% of patients with chronic obstructive pulmonary disease (COPD) also display characteristics of asthma. In May 2014, the asthma-COPD overlap syndrome (ACOS) was briefly addressed in the Global Initiative for Asthma (GINA) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy documents. We evaluated how pulmonologists diagnose and treat ACOS and how they assess its control. Pulmonologists from two university healthcare centers, having ≥ 1 year experience, treating patients with asthma, COPD, or ACOS, were invited to participate in focus groups. Two focus groups (1 hour duration) were convened with seven and five participants, respectively. According to pulmonologists from both institutions, ACOS is a new name for an existing syndrome rather than a new disease. It is characterized by incomplete reversible airflow limitations and changes in forced expiratory volume in one second over time. The pulmonologists noted that its diagnosis must be based on clinical characteristics, pulmonary function test results, and clinical intuition. To diagnose ACOS, pulmonologists must rely on their clinical judgment. They also agreed that the treatment of patients with ACOS should target the features of both asthma and COPD. Pulmonologists from both institutions used asthma control criteria to assess ACOS control. A deeper understanding would enable clinicians to establish specific criteria for the diagnosis, treatment, and follow-up of subjects with ACOS.

Community-Acquired Pneumonia in Latin America.

PubMed

Iannella, Hernán A; Luna, Carlos M

2016-12-01

Community-acquired pneumonia (CAP) is associated with significant morbidity and mortality in Latin America and the Caribbean (LAC) region. Poverty, socioeconomic factors, and malnutrition influence the incidence and outcome of CAP in LAC. In LAC, Streptococcus pneumoniae is the most frequent microorganism responsible for CAP, (incidence: 24-78%); the incidence of atypical microorganisms is similar to other regions of the world. Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) is a growing problem in the LAC region, with the Caribbean being the second most affected area worldwide after Sub-Saharan Africa. Pneumococcal pneumonia remains the most common cause of CAP in HIV-infected patients, but Pneumocystis jirovecii and tuberculosis (TB) are also common in this population. The heterogeneity of the health care systems and social inequity between different countries in LAC, and even between different settings inside the same country, is a difficult issue. TB, including multidrug-resistant TB, is several times more common in South American and Central American countries compared with North America. Furthermore, hantaviruses circulating in the Americas (new world hantaviruses) generate a severe respiratory disease called hantavirus pulmonary syndrome, with an associated mortality as high as 50%. More than 30 hantaviruses have been reported in the Western Hemisphere, with more frequent cases registered in the southern cone (Argentina, Chile, Uruguay, Paraguay, Bolivia, and Brazil). Respiratory viruses (particularly influenza) remain an important cause of morbidity and mortality, particularly in the elderly. Low rates of vaccination (against influenza as well as pneumococcus) may heighten the risk of these infections in low- and middle-income countries. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Hemorrhagic fever with renal syndrome and Crimean-Congo hemorrhagic fever as causes of acute undifferentiated febrile illness in Bulgaria.

PubMed

Christova, Iva; Younan, Rasha; Taseva, Evgenia; Gladnishka, Teodora; Trifonova, Iva; Ivanova, Vladislava; Spik, Kristin; Schmaljohn, Connie; Mohareb, Emad

2013-03-01

Hemorrhagic fever with renal syndrome (HFRS) and Crimean-Congo hemorrhagic fever (CCHF) are the 2 widespread viral hemorrhagic fevers occurring in Europe. HFRS is distributed throughout Europe, and CCHF has been reported mainly on the Balkan Peninsula and Russia. Both hemorrhagic fevers are endemic in Bulgaria. We investigated to what extent acute undifferentiated febrile illness in Bulgaria could be due to hantaviruses or to CCHF virus. Using enzyme-linked immunosorbent assays (ELISAs), we tested serum samples from 527 patients with acute febrile illness for antibodies against hantaviruses and CCHF virus. Immunoglobulin M (IgM) antibodies against hantaviruses were detected in 15 (2.8%) of the patients. Of the 15 hantavirus-positive patients, 8 (1.5%) were positive for Dobrava virus (DOBV), 5 (0.9%) were positive for Puumala virus (PUUV), and the remaining 2 were positive for both hantaviruses. A plaque reduction neutralization test (PRNT) confirmed 4 of the 10 DOBV-positive samples. PRNT was negative for all PUUV-positive samples. Serologic evidence of recent CCHF virus infection was found in 13 (2.5%) of the patients. Interestingly, HFRS and CCHF were not only detected in well-known endemic areas of Bulgaria but also in nonendemic regions. Our results suggested that in endemic countries, CCHF and/or HFRS might appear as a nonspecific febrile illness in a certain proportion of patients. Physicians must be aware of possible viral hemorrhagic fever cases, even if hemorrhages or renal impairment are not manifested.

Divergent ancestral lineages of newfound hantaviruses harbored by phylogenetically related crocidurine shrew species in Korea

PubMed Central

Arai, Satoru; Gu, Se Hun; Baek, Luck Ju; Tabara, Kenji; Bennett, Shannon; Oh, Hong-Shik; Takada, Nobuhiro; Kang, Hae Ji; Tanaka-Taya, Keiko; Morikawa, Shigeru; Okabe, Nobuhiko; Yanagihara, Richard; Song, Jin-Won

2012-01-01

Spurred by the recent isolation of a novel hantavirus, named Imjin virus (MJNV), from the Ussuri white-toothed shrew (Crocidura lasiura), targeted trapping was conducted for the phylogenetically related Asian lesser white-toothed shrew (Crocidura shantungensis). Pair-wise alignment and comparison of the S, M and L segments of a newfound hantavirus, designated Jeju virus (JJUV), indicated remarkably low nucleotide and amino acid sequence similarity with MJNV. Phylogenetic analyses, using maximum likelihood and Bayesian methods, showed divergent ancestral lineages for JJUV and MJNV, despite the close phylogenetic relationship of their reservoir soricid hosts. Also, no evidence of host switching was apparent in tanglegrams, generated by TreeMap 2.0β. PMID:22230701

[Transient expression and characterization of intracellular single chain Fv against the nucleocapsid protein of Hantavirus].

PubMed

Bai, Wen-tao; Xu, Zhi-kai; Zhang, Fang-lin; Luo, Wen; Liu, Yong; Wu, Xing-an; Yan, Yan

2004-11-01

To transiently express an intracellular single chain Fv of monoclonal antibody 1A8 against nucleocapsid protein of Hantavirus and characterize the immunological activities of the expressed products. COS-7 cells were transfected with mammalian expression vector 1A8-scFv-Ckappa/pCI-neo via lipofectin. The expressed product was identified by indirect immunofluorescence and immunoprecipitation. A diffuse pattern fluorescence was observed in less than 1% cytoplasm of transfected COS-7 cells. The binding of intracellular antibody fragments to NP antigen was confirmed by immunoprecipitation analysis. Transiently expressed single chain intrabodies can effectively target NP antigen in the cytoplasm. The present study may provide a new approach for treatment of Hantavirus.

High Prevalence of Tula Hantavirus in Common Voles in The Netherlands.

PubMed

Maas, Miriam; de Vries, Ankje; van Roon, Annika; Takumi, Katsuhisa; van der Giessen, Joke; Rockx, Barry

2017-03-01

Tula virus (TULV) is a zoonotic hantavirus. Knowledge about TULV in the Netherlands is very scarce. Therefore in 2014, 49 common voles (Microtus arvalis) from a region in the south of the Netherlands, and in 2015, 241 common voles from regions in the north of the Netherlands were tested with the TULV quantitative RT-PCR. In the southern region, prevalence of TULV was 41% (20/49). In the northern regions, prevalence ranged from 12% (4/34) to 45% (17/38). Phylogenetic analysis of the obtained sequences showed that the regions fall within different clusters. Voles from the south were also tested on-site for the presence of hantavirus antibodies, but serology results were poorly associated with qRT-PCR results. These findings suggest that TULV may be more widespread than previously thought. No human TULV cases have been reported thus far in the Netherlands, but differentiation between infection by TULV or the closely related Puumala virus is not made in humans in the Netherlands, thus cases may be misdiagnosed.

Increased pulmonary alveolar-capillary permeability in patients at risk for adult respiratory distress syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tennenberg, S.D.; Jacobs, M.P.; Solomkin, J.S.

1987-04-01

Two methods for predicting adult respiratory distress syndrome (ARDS) were evaluated prospectively in a group of 81 multitrauma and sepsis patients considered at clinical high risk. A popular ARDS risk-scoring method, employing discriminant analysis equations (weighted risk criteria and oxygenation characteristics), yielded a predictive accuracy of 59% and a false-negative rate of 22%. Pulmonary alveolar-capillary permeability (PACP) was determined with a radioaerosol lung-scan technique in 23 of these 81 patients, representing a statistically similar subgroup. Lung scanning achieved a predictive accuracy of 71% (after excluding patients with unilateral pulmonary contusion) and gave no false-negatives. We propose a combination of clinicalmore » risk identification and functional determination of PACP to assess a patient's risk of developing ARDS.« less

Dysregulation of Galectin-3. Implications for Hermansky-Pudlak Syndrome Pulmonary Fibrosis

PubMed Central

Cullinane, Andrew R.; Yeager, Caroline; Dorward, Heidi; Carmona-Rivera, Carmelo; Wu, Hai Ping; Moss, Joel; O’Brien, Kevin J.; Nathan, Steven D.; Meyer, Keith C.; Rosas, Ivan O.; Helip-Wooley, Amanda; Huizing, Marjan; Gahl, William A.

2014-01-01

The etiology of Hermansky-Pudlak syndrome (HPS) pulmonary fibrosis (HPSPF), a progressive interstitial lung disease with high mortality, is unknown. Galectin-3 is a β-galactoside–binding lectin with profibrotic effects. The objective of this study was to investigate the involvement of galectin-3 in HPSPF. Galectin-3 was measured by ELISA, immunohistochemistry, and immunoblotting in human specimens from subjects with HPS and control subjects. Mechanisms of galectin-3 accumulation were studied by quantitative RT-PCR, Northern blot analysis, membrane biotinylation assays, and rescue of HPS1-deficient cells by transfection. Bronchoalveolar lavage galectin-3 concentrations were significantly higher in HPSPF compared with idiopathic pulmonary fibrosis or that from normal volunteers, and correlated with disease severity. Galectin-3 immunostaining was increased in HPSPF compared with idiopathic pulmonary fibrosis or normal lung tissue. Fibroblasts from subjects with HPS subtypes associated with pulmonary fibrosis had increased galectin-3 protein expression compared with cells from nonfibrotic HPS subtypes. Galectin-3 protein accumulation was associated with reduced Galectin-3 mRNA, normal Mucin 1 levels, and up-regulated microRNA-322 in HPSPF cells. Membrane biotinylation assays showed reduced galectin-3 and normal Mucin 1 expression at the plasma membrane in HPSPF cells compared with control cells, which suggests that galectin-3 is mistrafficked in these cells. Reconstitution of HPS1 cDNA into HPS1-deficient cells normalized galectin-3 protein and mRNA levels, as well as corrected galectin-3 trafficking to the membrane. Intracellular galectin-3 levels are regulated by HPS1 protein. Abnormal accumulation of galectin-3 may contribute to the pathogenesis of HPSPF. PMID:24134621

Lung ultrasonography of pulmonary complications in preterm infants with respiratory distress syndrome.

PubMed

Lovrenski, Jovan

2012-03-01

To evaluate the diagnostic possibilities of lung ultrasonography (LUS) in detecting pulmonary complications in preterm infants with respiratory distress syndrome (RDS). A prospective study included 120 preterm infants with clinical and radiographic signs of RDS. LUS was performed using both a transthoracic and a transabdominal approach within the first 24 h of life, and, after that, follow-up LUS examinations were performed. In 47 detected pulmonary complications of RDS (hemorrhage, pneumothorax, pneumonia, atelectasis, bronchopulmonary dysplasia), comparisons between LUS and chest X-ray (CXR) were made. Also, 90 subpleural consolidations registered during LUS examinations were analysed. Statistical analysis included MANOVA and discriminant analysis, t-test, confidence interval, and positive predictive value. In 45 of 47 instances the same diagnosis of complication was detected with LUS as with CXR, indicating a high reliability of the method in premature infants with RDS. The only two false negative findings concerned partial pneumothorax. The positive predictive value of LUS was 100%. A statistically significant difference of LUS findings between the anterior and posterior lung areas was observed in both right and left hemithoraces. LUS enables the detection of pulmonary complications in preterm infants with RDS and has the potential to reduce the number of CXRs. The specific guidelines for its use should be provided in a more extensive study.

Selective predation on hantavirus-infected voles by owls and confounding effects from landscape properties.

PubMed

Khalil, Hussein; Ecke, Frauke; Evander, Magnus; Hörnfeldt, Birger

2016-06-01

It has been suggested that predators may protect human health through reducing disease-host densities or selectively preying on infected individuals from the population. However, this has not been tested empirically. We hypothesized that Tengmalm's owl (Aegolius funereus) selectively preys on hantavirus-infected individuals of its staple prey, the bank vole (Myodes glareolus). Bank voles are hosts of Puumala hantavirus, which causes a form of hemorrhagic fever in humans. Selective predation by owls on infected voles may reduce human disease risk. We compared the prevalence of anti-Puumala hantavirus antibodies (seroprevalence), in bank voles cached by owls in nest boxes to seroprevalence in voles trapped in closed-canopy forest around each nest box. We found no general difference in seroprevalence. Forest landscape structure could partly account for the observed patterns in seroprevalence. Only in more connected forest patches was seroprevalence in bank voles cached in nest boxes higher than seroprevalence in trapped voles. This effect disappeared with increasing forest patch isolation, as seroprevalence in trapped voles increased with forest patch isolation, but did not in cached voles. Our results suggest a complex relationship between zoonotic disease prevalence in hosts, their predators, and landscape structure. Some mechanisms that may have caused the seroprevalence patterns in our results include higher bank vole density in isolated forest patches. This study offers future research potential to shed further light on the contribution of predators and landscape properties to human health.

Platelet abnormalities in adults with severe pulmonary arterial hypertension related to congenital heart defects (Eisenmenger syndrome).

PubMed

Remková, Anna; Šimková, Iveta; Valkovičová, Tatiana; Kaldarárová, Monika

2016-12-01

Patients with severe pulmonary arterial hypertension suffer from life-threatening thrombotic and bleeding complications. The aim of this study was to compare selected platelet, endothelial, and coagulation parameters in healthy volunteers and patients with severe pulmonary arterial hypertension because of congenital heart defects. The study included healthy volunteers (n = 50) and patients with cyanotic congenital heart defects classified as Eisenmenger syndrome (n = 41). We investigated platelet count, mean platelet volume, and platelet aggregation - spontaneous and induced by various concentrations of five agonists. Von Willebrand factor (vWF), fibrinogen, factor VIII and XII, plasminogen activator inhibitor, antithrombin, D-dimer, and antiphospholipid antibodies were also investigated. We found a decreased platelet count [190 (147-225) vs. 248 (205-295) 10 l, P < 0.0001], higher mean platelet volume [10.9 (10.1-12.0) vs. 10.2 (9.4-10.4) fl, P < 0.0001], and significantly decreased platelet aggregation (induced by five agonists, in various concentrations) in patients with Eisenmenger syndrome compared with controls. These changes were accompanied by an increase of plasma vWF antigen [141.6 (108.9-179.1) vs. 117.4 (9.2-140.7) IU/dl, P = 0.022] and serum anti-β2-glycoprotein [2.07 (0.71-3.41) vs. 0.47 (0.18-0.99) U/ml, P < 0.0001]. Eisenmenger syndrome is accompanied by platelet abnormalities. Thrombocytopenia with increased platelet size is probably due to a higher platelet turnover associated with platelet activation. Impaired platelet aggregation can reflect specific platelet behaviour in patients with Eisenmenger syndrome. These changes can be related both to bleeding and to thrombotic events. A higher vWF antigen may be a consequence of endothelial damage in Eisenmenger syndrome, but the cause for an increase of anti-β2-glycoprotein is unknown.

Experimental evaluation of rodent exclusion methods to reduce hantavirus transmission to residents in a Native American community in New Mexico.

PubMed

Hopkins, Andrew S; Whitetail-Eagle, Joe; Corneli, Amy L; Person, Bobbie; Ettestad, Paul J; DiMenna, Mark; Norstog, Jon; Creswell, Jacob; Khan, Ali S; Olson, James G; Cavallaro, Kathleen F; Bryan, Ralph T; Cheek, James E; Begay, Bruce; Hoddenbach, Gerard A; Ksiazek, Thomas G; Mills, James N

2002-01-01

We conducted a pilot study to evaluate the efficacy of rodent proofing continuously occupied homes as a method for lowering the risk for hantavirus pulmonary syndrome (HPS) among residents of a Native American community in northwestern New Mexico. Rodent proofing of dwellings was paired with culturally appropriate health education. Seventy homes were randomly assigned to treatment or control categories. Treatment homes were rodent-proofed by sealing openings around foundations, doors, roofs, and pipes and repairing screens and windows. Repairs to each dwelling were limited to $500 US. After repairs were completed, 15-20 snap traps were placed in each treatment and control home and checked approximately every 2 days for an average of 3-4 weeks. During 23,373 trap nights, one house mouse (Mus musculus) was captured in one treatment home, and 20 mice (16 deer mice, Peromyscus maniculatus, two Pinyon mice, Peromyscus truei, and two unidentified mice) were captured in five control homes (one house had 14 captures, two had two captures, and two had one capture). Trap success was 0.01% in treatment homes and 0.15% in controls. Intensity of infestation (mean number of mice captured per infested home) was 1 in treatment homes and 4 in controls. Observations of evidence of infestation (feces, nesting material, gnaw marks, or reports of infestation by occupant) per 100 days of observation were 1.2 in treatment homes and 3.1 in controls. Statistical power of the experiment was limited because it coincided with a period of low rodent abundance (August-November 2000). Nevertheless, these results suggest that inexpensive rodent proofing of occupied rural homes can decrease the frequency and intensity of rodent intrusion, thereby reducing the risk of HPS among rural residents in the southwestern United States.

Ectopic Cushing's syndrome and pulmonary carcinoid tumour identified by [111In-DTPA-D-Phe1]octreotide.

PubMed Central

Matte, J.; Roufosse, F.; Rocmans, P.; Schoutens, A.; Jacobovitz, D.; Mockel, J.

1998-01-01

The differential diagnosis and management of Cushing's syndrome remain difficult, particularly for ectopic adrenocorticotropin (ACTH) syndromes resulting from small bronchial carcinoids. We report the case of a 41-year-old man with ectopic ACTH-dependent Cushing's syndrome. Two computed tomography scans of the thorax were normal and magnetic resonance imaging of the chest showed a 6-mm hyperintense T1-weighted area close to the left pulmonary hilus, interpreted as probably vascular by the radiologists. An [111In-DTPA-D-Phe1]octreotide scintigraphy scan demonstrated a positive image for somatostatin receptors in exactly the same location and surgery confirmed the presence of a small ACTH-secreting carcinoid tumour in the upper left lung lobe which was resected. Surgery cured the hypercorticism of the patient. The differential diagnosis of Cushing's syndrome and the procedure for localisation of an ACTH source are discussed. Images Figure PMID:9616493

Andes Hantavirus-Infection of a 3D Human Lung Tissue Model Reveals a Late Peak in Progeny Virus Production Followed by Increased Levels of Proinflammatory Cytokines and VEGF-A

PubMed Central

Sundström, Karin B.; Nguyen Hoang, Anh Thu; Gupta, Shawon; Ahlm, Clas; Svensson, Mattias; Klingström, Jonas

2016-01-01

Andes virus (ANDV) causes hantavirus pulmonary syndrome (HPS), a severe acute disease with a 40% case fatality rate. Humans are infected via inhalation, and the lungs are severely affected during HPS, but little is known regarding the effects of ANDV-infection of the lung. Using a 3-dimensional air-exposed organotypic human lung tissue model, we analyzed progeny virus production and cytokine-responses after ANDV-infection. After a 7–10 day period of low progeny virus production, a sudden peak in progeny virus levels was observed during approximately one week. This peak in ANDV-production coincided in time with activation of innate immune responses, as shown by induction of type I and III interferons and ISG56. After the peak in ANDV production a low, but stable, level of ANDV progeny was observed until 39 days after infection. Compared to uninfected models, ANDV caused long-term elevated levels of eotaxin-1, IL-6, IL-8, IP-10, and VEGF-A that peaked 20–25 days after infection, i.e., after the observed peak in progeny virus production. Notably, eotaxin-1 was only detected in supernatants from infected models. In conclusion, these findings suggest that ANDV replication in lung tissue elicits a late proinflammatory immune response with possible long-term effects on the local lung cytokine milieu. The change from an innate to a proinflammatory response might be important for the transition from initial asymptomatic infection to severe clinical disease, HPS. PMID:26907493

Andes Hantavirus-Infection of a 3D Human Lung Tissue Model Reveals a Late Peak in Progeny Virus Production Followed by Increased Levels of Proinflammatory Cytokines and VEGF-A.

PubMed

Sundström, Karin B; Nguyen Hoang, Anh Thu; Gupta, Shawon; Ahlm, Clas; Svensson, Mattias; Klingström, Jonas

2016-01-01

Andes virus (ANDV) causes hantavirus pulmonary syndrome (HPS), a severe acute disease with a 40% case fatality rate. Humans are infected via inhalation, and the lungs are severely affected during HPS, but little is known regarding the effects of ANDV-infection of the lung. Using a 3-dimensional air-exposed organotypic human lung tissue model, we analyzed progeny virus production and cytokine-responses after ANDV-infection. After a 7-10 day period of low progeny virus production, a sudden peak in progeny virus levels was observed during approximately one week. This peak in ANDV-production coincided in time with activation of innate immune responses, as shown by induction of type I and III interferons and ISG56. After the peak in ANDV production a low, but stable, level of ANDV progeny was observed until 39 days after infection. Compared to uninfected models, ANDV caused long-term elevated levels of eotaxin-1, IL-6, IL-8, IP-10, and VEGF-A that peaked 20-25 days after infection, i.e., after the observed peak in progeny virus production. Notably, eotaxin-1 was only detected in supernatants from infected models. In conclusion, these findings suggest that ANDV replication in lung tissue elicits a late proinflammatory immune response with possible long-term effects on the local lung cytokine milieu. The change from an innate to a proinflammatory response might be important for the transition from initial asymptomatic infection to severe clinical disease, HPS.

Clinical management and outcomes of patients with Hermansky-Pudlak syndrome pulmonary fibrosis evaluated for lung transplantation

PubMed Central

El-Chemaly, Souheil; O’Brien, Kevin J.; Nathan, Steven D.; Weinhouse, Gerald L.; Goldberg, Hilary J.; Connors, Jean M.; Cui, Ye; Astor, Todd L.; Camp, Philip C.; Rosas, Ivan O.; Lemma, Merte; Speransky, Vladislav; Merideth, Melissa A.; Gahl, William A.

2018-01-01

Pulmonary fibrosis is a progressive, fatal manifestation of Hermansky-Pudlak syndrome (HPS). Some patients with advanced HPS pulmonary fibrosis undergo lung transplantation despite their disease-associated bleeding tendency; others die while awaiting donor organs. The objective of this study is to determine the clinical management and outcomes of a cohort with advanced HPS pulmonary fibrosis who were evaluated for lung transplantation. Six patients with HPS-1 pulmonary fibrosis were evaluated at the National Institutes of Health Clinical Center and one of two regional lung transplant centers. Their median age was 41.5 years pre-transplant. Three of six patients died without receiving a lung transplant. One of these was referred with end-stage pulmonary fibrosis and died before a donor organ became available, and donor organs were not identified for two other patients sensitized from prior blood product transfusions. Three of six patients received bilateral lung transplants; they did not have a history of excessive bleeding. One patient received peri-operative desmopressin, one was transfused with intra-operative platelets, and one received extracorporeal membrane oxygenation and intra-operative prothrombin complex concentrate, platelet transfusion, and desmopressin. One transplant recipient experienced acute rejection that responded to pulsed steroids. No evidence of chronic lung allograft dysfunction or recurrence of HPS pulmonary fibrosis was detected up to 6 years post-transplant in these three lung transplant recipients. In conclusion, lung transplantation and extracorporeal membrane oxygenation are viable options for patients with HPS pulmonary fibrosis. Alloimmunization in HPS patients is an important and potentially preventable barrier to lung transplantation; interventions to limit alloimmunization should be implemented in HPS patients at risk of pulmonary fibrosis to optimize their candidacy for future lung transplants. PMID:29547626

Clinical management and outcomes of patients with Hermansky-Pudlak syndrome pulmonary fibrosis evaluated for lung transplantation.

PubMed

El-Chemaly, Souheil; O'Brien, Kevin J; Nathan, Steven D; Weinhouse, Gerald L; Goldberg, Hilary J; Connors, Jean M; Cui, Ye; Astor, Todd L; Camp, Philip C; Rosas, Ivan O; Lemma, Merte; Speransky, Vladislav; Merideth, Melissa A; Gahl, William A; Gochuico, Bernadette R

2018-01-01

Pulmonary fibrosis is a progressive, fatal manifestation of Hermansky-Pudlak syndrome (HPS). Some patients with advanced HPS pulmonary fibrosis undergo lung transplantation despite their disease-associated bleeding tendency; others die while awaiting donor organs. The objective of this study is to determine the clinical management and outcomes of a cohort with advanced HPS pulmonary fibrosis who were evaluated for lung transplantation. Six patients with HPS-1 pulmonary fibrosis were evaluated at the National Institutes of Health Clinical Center and one of two regional lung transplant centers. Their median age was 41.5 years pre-transplant. Three of six patients died without receiving a lung transplant. One of these was referred with end-stage pulmonary fibrosis and died before a donor organ became available, and donor organs were not identified for two other patients sensitized from prior blood product transfusions. Three of six patients received bilateral lung transplants; they did not have a history of excessive bleeding. One patient received peri-operative desmopressin, one was transfused with intra-operative platelets, and one received extracorporeal membrane oxygenation and intra-operative prothrombin complex concentrate, platelet transfusion, and desmopressin. One transplant recipient experienced acute rejection that responded to pulsed steroids. No evidence of chronic lung allograft dysfunction or recurrence of HPS pulmonary fibrosis was detected up to 6 years post-transplant in these three lung transplant recipients. In conclusion, lung transplantation and extracorporeal membrane oxygenation are viable options for patients with HPS pulmonary fibrosis. Alloimmunization in HPS patients is an important and potentially preventable barrier to lung transplantation; interventions to limit alloimmunization should be implemented in HPS patients at risk of pulmonary fibrosis to optimize their candidacy for future lung transplants.

Abnormal neutrophil-pulmonary interaction in the adult respiratory distress syndrome. Qualitative and quantitative assessment of pulmonary neutrophil kinetics in humans with in vivo /sup 111/indium neutrophil scintigraphy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warshawski, F.J.; Sibbald, W.J.; Driedger, A.A.

1986-05-01

In the absence of direct toxins, the majority of evidence from animal models suggests that neutrophils (PMN) are necessary for the full expression of the abnormal pulmonary permeability accompanying acute microvascular lung injury. We therefore studied the role of the PMN in the human correlate of this disease, the adult respiratory distress syndrome (ARDS), by assessing the pulmonary retention of infused autologous /sup 111/Indium-labeled PMN (PMN-In). We evaluated 79 patients, prospectively categorized as: active ARDS (Aa; n = 30), active ARDS and concurrent corticosteroid therapy (As; n = 11), resolving ARDS (Ar; n = 13), sepsis without pulmonary edema (S;more » n = 7), and cardiac pulmonary edema (C; n = 18). This clinical separation was confirmed by retrospective analysis of associated measures of hemodynamic and respiratory dysfunction. We found that both analog scintigrams (positive/negative for diffuse pulmonary PMN-In sequestration) and computer-assisted quantitative analysis in 46 patients (T 1/2 of first hour demargination and percentage of peak activity/pixel/second remaining at 17 to 20 h) showed a significant rank order decrease in the pulmonary retention of labeled PMN-In through the Groups Aa----As----S----Ar----C. Our findings recognized aspects of in vivo PMN-In behavior that implied pathophysiologic differences between groups of critically ill patients in either the PMN themselves or in PMN-pulmonary endothelial interaction. This demonstrates the possibility of abnormal in vivo PMN-endothelial interaction in ARDS by virtue of the greater pulmonary localization of PMN in active ARDS versus resolving disease, septic non-ARDS states, and cardiac pulmonary edema.« less

[Effect of the components of the metabolic syndrome on pulmonary function. The unexpected role of high-density lipoprotein cholesterol].

PubMed

Huerta-Ramírez, Saúl; Paniagua-Pérez, Angélica; Castro-Serna, David; Ledesma-Velázquez, Andrés; Rubio-Guerra, Alberto; Vargas-Ayala, Germán

2018-01-01

Metabolic syndrome is a condition that predisposes to cardiovascular disease and diabetes mellitus. In addition, it can have effects over neoplastic pathologies, liver and pulmonary function. Our objective is to analyze the effect of the metabolic syndrome and its components on pulmonary function. 110 subjects from Mexico City were evaluated and anthropometric measurements, glucose determination, triglycerides and high-density lipoprotein (HDL) cholesterol were made. They underwent a simple spirometry. Diagnosis of metabolic syndrome was made following the NCEP-ATPIII criteria. Of 110 individuals, 90 (82%) were women and 20 men (18%); 71 subjects (65%) presented metabolic syndrome. Subjects with central obesity had a forced vital capacity (FVC) lower than subjects without central obesity (2.72 vs. 3.11 liters; p < 0.05). Those with low HDL had better spirometric results than subjects with normal HDL (FEV1 2.36 vs. 1.85 liters; p < 0.05), FVC (2.95 vs. 2.45 liters; p < 0.05) and FEV1/FVC ratio (0.78 vs.74; p < 0.05). Hypertensive subjects presented lower volumes in FEV1 (1.91 vs. 2.38; p < 0.05) and FVC (2.49 vs. 2.99; p < 0.05). There is no difference between the spirometry volumes of patients with metabolic syndrome versus the metabolically healthy subjects. The only factors associated with a decrease in FEV1 and FVC are central obesity and arterial hypertension. An unexpected finding was the negative correlation between HDL levels and lung function. Copyright: © 2018 Permanyer.

Deregulation of levels of angiopoietin-1 and angiopoietin-2 is associated with severe courses of hantavirus infection.

PubMed

Nusshag, Christian; Osberghaus, Anja; Baumann, Alexandra; Schnitzler, Paul; Zeier, Martin; Krautkrämer, Ellen

2017-09-01

Hantavirus disease is characterized by endothelial dysfunction. Angiopoietin-1 (Ang-1) and its antagonist angiopoietin-2 (Ang-2) play a key role in the control of capillary permeability. Ang-1 is responsible for maintenance of cell-to-cell contacts whereas Ang-2 destabilizes monolayers. An imbalance of Ang-1 and Ang-2 levels results in enhanced permeability and capillary leakage. To analyze the involvement of angiopoietins in hantavirus-induced disruption of endothelia, we measured the levels of Ang-1 and Ang-2 in hantavirus infection. Levels of angiopoietins of 31 patients with acute Puumala virus (PUUV) infection and a patient infected with Dobrava-Belgrade virus genotype Sochi (DOBV-Sochi) were analyzed. An age-matched group of 16 healthy volunteers served as control. The ratios of Ang-2 to Ang-1 levels were calculated and correlated with laboratory parameters. Patients with PUUV and DOBV-Sochi infection exhibited elevated ratios of Ang-2/Ang-1 compared to the control group. The imbalance of Ang-2 to Ang-1 levels was observed early after onset of symptoms and lasted for the acute phase of infection. The deregulation in DOBV-Sochi infection was more prominent than in PUUV infection. Analysis of Ang-2/Ang-1 ratio and laboratory parameters in the PUUV cohort revealed a positive correlation with serum creatinine and a negative correlation with serum albumin and thrombocyte levels. We observed an imbalance between levels of Ang-1 and Ang-2 in patients infected with PUUV and DOBV-Sochi. Elevated Ang-2/Ang-1 ratios correlate with disease severity. The virus-induced deregulation of angiopoietin levels may enhance capillary permeability and contribute to the pathogenesis of hantavirus disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Pulmonary capillary pressure in pulmonary hypertension.

PubMed

Souza, Rogerio; Amato, Marcelo Britto Passos; Demarzo, Sergio Eduardo; Deheinzelin, Daniel; Barbas, Carmen Silvia Valente; Schettino, Guilherme Paula Pinto; Carvalho, Carlos Roberto Ribeiro

2005-04-01

Pulmonary capillary pressure (PCP), together with the time constants of the various vascular compartments, define the dynamics of the pulmonary vascular system. Our objective in the present study was to estimate PCPs and time constants of the vascular system in patients with idiopathic pulmonary arterial hypertension (IPAH), and compare them with these measures in patients with acute respiratory distress syndrome (ARDS). We conducted the study in two groups of patients with pulmonary hypertension: 12 patients with IPAH and 11 with ARDS. Four methods were used to estimate the PCP based on monoexponential and biexponential fitting of pulmonary artery pressure decay curves. PCPs in the IPAH group were considerably greater than those in the ARDS group. The PCPs measured using the four methods also differed significantly, suggesting that each method measures the pressure at a different site in the pulmonary circulation. The time constant for the slow component of the biexponential fit in the IPAH group was significantly longer than that in the ARDS group. The PCP in IPAH patients is greater than normal but methodological limitations related to the occlusion technique may limit interpretation of these data in isolation. Different disease processes may result in different times for arterial emptying, with resulting implications for the methods available for estimating PCP.

Spatiotemporal dynamics of Puumala hantavirus associated with its rodent host, Myodes glareolus

PubMed Central

Weber de Melo, Vanessa; Sheikh Ali, Hanan; Freise, Jona; Kühnert, Denise; Essbauer, Sandra; Mertens, Marc; Wanka, Konrad M; Drewes, Stephan; Ulrich, Rainer G; Heckel, Gerald

2015-01-01

Many viruses significantly impact human and animal health. Understanding the population dynamics of these viruses and their hosts can provide important insights for epidemiology and virus evolution. Puumala virus (PUUV) is a European hantavirus that may cause regional outbreaks of hemorrhagic fever with renal syndrome in humans. Here, we analyzed the spatiotemporal dynamics of PUUV circulating in local populations of its rodent reservoir host, the bank vole (Myodes glareolus) during eight years. Phylogenetic and population genetic analyses of all three genome segments of PUUV showed strong geographical structuring at a very local scale. There was a high temporal turnover of virus strains in the local bank vole populations, but several virus strains persisted through multiple years. Phylodynamic analyses showed no significant changes in the local effective population sizes of PUUV, although vole numbers and virus prevalence fluctuated widely. Microsatellite data demonstrated also a temporally persisting subdivision between local vole populations, but these groups did not correspond to the subdivision in the virus strains. We conclude that restricted transmission between vole populations and genetic drift play important roles in shaping the genetic structure and temporal dynamics of PUUV in its natural host which has several implications for zoonotic risks of the human population. PMID:26136821

Right Atrial Anomalous Muscle Bundle Presenting with Acute Superior Vena Cava Syndrome and Pulmonary Embolism: Surgical Management.

PubMed

Madjarov, Jeko M; Katz, Michael G; Madjarova, Sophia; Madzharov, Svetozar; Arko, Frank R; Miller, David W; Robicsek, Francis

2018-05-21

An anomalous muscle bundle crossing the right atrial cavity represents a pathological finding with unproved clinical significance. This congenital anomaly may be difficult to recognize via echocardiography and could be confused with other intra-cavitary lesions. We report a case of a 53-year-old female presented to the cardio-vascular service with acute superior vena cava syndrome and sub-massive pulmonary embolism. The patient underwent venography confirming superior vena cava stenosis. A ventilation/perfusion lung scan showed two sizable perfusion defects due to pulmonary embolism. MRI and echocardiography imaging demonstrated right atrium mass. Surgery was then carried out using standard cardiopulmonary bypass; right atrial muscle bundle was excised and superior vena cava reconstruction was performed. The patient was discharged uneventfully and remains symptom-free at two years follow-up. In cases of nonmalignant pathology of superior vena cava syndrome, appropriate studies should be conducted to exclude potential congenital abnormalities such as this anomalous muscle bundle in the right atrium. Open heart surgery is a viable treatment option in select cases. Published by Elsevier Inc.

From neurogenic pulmonary edema to fat embolism syndrome: a brief review of experimental and clinical investigations of acute lung injury and acute respiratory distress syndrome.

PubMed

Chen, Hsing I

2009-11-30

Acute respiratory distress syndrome (ARDS) is the most devastating form of acute lung injury (ALI) or pulmonary edema (PE). We presented the experimental studies and clinical investigations of two serious forms of ALI. Drastic and severe PE could be induced by intracranial hypertension or cerebral compression (CC). The CC-induced PE was attributed to overactivation of the medullary sympathetic mechanism. Sympathetic vasoconstriction of the systemic and pulmonary resistance and capacitance vessels caused shift of blood volume from the splanchnic vascular beds to the lung. The hemodynamic changes led to systemic and pulmonary hypertension. Consequently, left ventricular failure as evidenced by dramatic decline in aortic flow with a slow decrease in pulmonary flow resulted in pressure and volume loading in the pulmonary circulation. These changes finally produced severe alveolar flooding and sudden death. Vasodilators such as sodium nitroprusside or nitroglycerin were capable of reducing the CC-induced pulmonary pathology and hemodynamic alterations. Fat embolism syndrome (FES) is a serious clinical problem in patients suffering from long bone fractures. ARDS may develop and cause mortality. Our laboratory reported a total of 14 subjects associated with FES and died of ARDS. We also developed a simple technique to produce FES. Corn oil was mixed with distilled water to form fatty micelles. Intravenous administration of or introduction of fatty micelles in anesthetized rats or isolated perfused lungs caused severe alveolar damage. Our clinical observation and animal experimentation revealed that infusion of fatty acids caused physical phase, resulting in microvascular obstruction accompanied by pulmonary hypertension and increased capillary permeability. Thereafter, the lipases in the lung hydrolyzed the neutral fat and released free fatty acids and biochemical mediators which were toxic to the lung. Our data have suggested that nitric oxide (NO), inducible NO synthase

Person-to-Person Transmission of Andes Virus

PubMed Central

Bellomo, Carla; San Juan, Jorge; Pinna, Diego; Forlenza, Raul; Elder, Malco; Padula, Paula J.

2005-01-01

Despite the fact that rodents are considered to be the infectious source of hantavirus for humans, another route of transmission was demonstrated. Andes virus (ANDV) has been responsible for most of the cases recorded in Argentina. Person-to-person transmission of ANDV Sout lineage was described during an outbreak of hantavirus pulmonary syndrome in southwest Argentina. In this study, we analyzed 4 clusters that occurred in 2 disease-endemic areas for different ANDV lineages. We found new evidence of interhuman transmission for ANDV Sout lineage and described the first event in which another lineage, ANDV Cent BsAs, was implicated in this mechanism of transmission. On the basis of epidemiologic and genetic data, we concluded that person-to-person spread of the virus likely took place during the prodromal phase or shortly after it ended, since close and prolonged contact occurred in the events analyzed here, and the incubation period was 15–24 days. PMID:16485469

Asthma-chronic obstructive pulmonary disease overlap syndrome in Poland. Findings of an epidemiological study.

PubMed

Brzostek, Dorota; Kokot, Marek

2014-12-01

Recent years have seen an increased interest in asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS). In 2012, Takeda Polska conducted a non-interventional epidemiological study aimed at identifying the typical phenotype of ACOS patients receiving pulmonary care. The study enrolled a total of 12,103 of smoking patients above 45 years of age (mean age: 61.5 years; mean duration of smoking: 28.4 pack-years). A total of 68.6% of patients represented the frequent-exacerbation phenotype (mean number of exacerbations during 12 months: 2.11), and 56.4% of patients from the group comprising 12,103 participants were hospitalized at least once during their lifetime due to a respiratory system disease (mean number: 3.82 ±3.76). The most commonly found asthma symptoms included paroxysmal dyspnoea with wheezing, and good response to inhaled steroids. The most frequently identified COPD-associated symptoms were: long-lasting reduction in forced expiratory volume in 1 s (FEV1) (< 80% after administering a bronchodilator) and chronic productive cough. Eighty-five percent of patients were diagnosed with concomitant diseases, predominantly arterial hypertension (62.9%) and metabolic diseases (metabolic syndrome, obesity, type 2 diabetes - 46.4% in total). A clinically severe course of ACOS and the presence of concomitant diseases should be regarded as factors justifying an individual selection of inhalation therapy which specifically takes into account anti-inflammatory treatment and patient safety.

High-resolution computed tomography findings of acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis.

PubMed

Ichikado, Kazuya

2014-02-01

Diffuse alveolar damage (DAD) is the pathologic feature of rapidly progressive lung diseases, including acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis. The clinical significance and limitation of high-resolution computed tomography (HRCT) findings in these diseases were reviewed. The HRCT findings correlate well with pathologic phases (exudative, proliferative, and fibrotic) of DAD, although it cannot detect early exudative phase. Traction bronchiolectasis or bronchiectasis within areas of increased attenuation on HRCT scan is a sign of progression from the exudative to the proliferative and fibrotic phase of DAD. Extensive abnormalities seen on HRCT scans, which are indicative of fibroproliferative changes, were independently predictive of poor prognosis in patients with clinically early acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis. © 2013 Published by Elsevier Inc.

The relationship between physical activity and metabolic syndrome in people with chronic obstructive pulmonary disease.

PubMed

Park, Soo Kyung; Larson, Janet L

2014-01-01

The prevalence of metabolic syndrome has been reported to be 20% to 50% in people with chronic obstructive pulmonary disease (COPD). Because such people are sedentary and physically inactive, they are at risk of metabolic syndrome. The extent of this problem, however, is not fully understood. This study examined the relationship of sedentary time and physical activity to metabolic syndrome and the components of metabolic syndrome in a population-based sample of people with COPD. This was a secondary analysis of existing cross-sectional data. Subjects with COPD (n = 223) were drawn from the National Health and Nutrition Examination Survey data set (2003-2006). Physical activity was measured by accelerometry. Waist circumference, triglyceride level, high-density lipoprotein cholesterol level, blood pressure, and fasting glucose level were used to describe metabolic syndrome. Descriptive and inferential statistics were used for analysis. Fifty-five percent of the sample had metabolic syndrome. No significant differences in sedentary time and level of physical activity were found in people with COPD and metabolic syndrome and people with COPD only. However, those with a mean activity count of greater than 240 counts per minute had a lower prevalence of metabolic syndrome. Waist circumference and glucose level were significantly associated with the time spent in sedentary, light, and moderate to vigorous physical activity. Metabolic syndrome is highly prevalent in people with COPD, and greater physical activity and less sedentary time are associated with lower rates of metabolic syndrome. This suggests that interventions to decrease the risk of metabolic syndrome in people with COPD should include both reducing sedentary time and increasing the time and intensity of physical activity.

Chest sonography: a useful tool to differentiate acute cardiogenic pulmonary edema from acute respiratory distress syndrome

PubMed Central

Copetti, Roberto; Soldati, Gino; Copetti, Paolo

2008-01-01

Background Differential diagnosis between acute cardiogenic pulmonary edema (APE) and acute lung injury/acute respiratory distress syndrome (ALI/ARDS) may often be difficult. We evaluated the ability of chest sonography in the identification of characteristic pleuropulmonary signs useful in the diagnosis of ALI/ARDS and APE. Methods Chest sonography was performed on admission to the intensive care unit in 58 consecutive patients affected by ALI/ARDS or by acute pulmonary edema (APE). Results Ultrasound examination was focalised on finding in the two groups the presence of: 1) alveolar-interstitial syndrome (AIS) 2) pleural lines abnormalities 3) absence or reduction of "gliding" sign 4) "spared areas" 5) consolidations 6) pleural effusion 7) "lung pulse". AIS was found in 100% of patients with ALI/ARDS and in 100% of patients with APE (p = ns). Pleural line abnormalities were observed in 100% of patients with ALI/ARDS and in 25% of patients with APE (p < 0.0001). Absence or reduction of the 'gliding sign' was observed in 100% of patients with ALI/ARDS and in 0% of patients with APE. 'Spared areas' were observed in 100% of patients with ALI/ARDS and in 0% of patients with APE (p < 0.0001). Consolidations were present in 83.3% of patients with ALI/ARDS in 0% of patients with APE (p < 0.0001). A pleural effusion was present in 66.6% of patients with ALI/ARDS and in 95% of patients with APE (p < 0.004). 'Lung pulse' was observed in 50% of patients with ALI/ARDS and in 0% of patients with APE (p < 0.0001). All signs, except the presence of AIS, presented a statistically significant difference in presentation between the two syndromes resulting specific for the ultrasonographic characterization of ALI/ARDS. Conclusion Pleuroparenchimal patterns in ALI/ARDS do find a characterization through ultrasonographic lung scan. In the critically ill the ultrasound demonstration of a dyshomogeneous AIS with spared areas, pleural line modifications and lung consolidations is

Pulmonary hypertension and hepatic cirrhosis.

PubMed

Téllez Villajos, L; Martínez González, J; Moreira Vicente, V; Albillos Martínez, A

2015-01-01

Pulmonary hypertension is a relatively common phenomenon in patients with hepatic cirrhosis and can appear through various mechanisms. The most characteristic scenario that binds portal and pulmonary hypertension is portopulmonary syndrome. However, hyperdynamic circulation, TIPS placement and heart failure can raise the mean pulmonary artery pressure without increasing the resistances. These conditions are not candidates for treatment with pulmonary vasodilators and require a specific therapy. A correct assessment of hemodynamic, ultrasound and clinical variables enables the differential diagnosis of each situation that produces pulmonary hypertension in patients with cirrhosis. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Sequential occurrence of combined pulmonary fibrosis and emphysema syndrome in a non-smoker female patient.

PubMed

Gupta, Pawan; Dash, Devijyoti; Mittal, Richa; Chhabra, Sunil K

2017-05-01

The combined pulmonary fibrosis and emphysema (CPFE) syndrome is a unique and an under-recognized disorder characterized by emphysema in the upper lobes and interstitial fibrosis in the lower lobes of the lung. It occurs predominantly in males and almost exclusively in smokers. This rare combination of a restrictive and an obstructive mechanical defect carries a poorer prognosis than either of the two components. We present a case of CPFE syndrome in a non-smoker female patient who developed lower lobe emphysema subsequent to development of interstitial fibrosis. The case was remarkable for the extreme rarity of several presenting features, namely, a lower lobe occurrence of emphysema subsequent to pre-existent interstitial fibrosis, female gender and absence of a history of smoking. © 2015 John Wiley & Sons Ltd.

Role of splenic reservoir monocytes in pulmonary vascular monocyte accumulation in experimental hepatopulmonary syndrome

PubMed Central

Wu, Wei; Zhang, Junlan; Yang, Wenli; Hu, Bingqian

2016-01-01

Abstract Background and Aim Pulmonary monocyte infiltration plays a significant role in the development of angiogenesis in experimental hepatopulmonary syndrome (HPS) after common bile duct ligation (CBDL). Hepatic monocytes are also increased after CBDL, but the origins remain unclear. Splenic reservoir monocytes have been identified as a major source of monocytes that accumulate in injured tissues. Whether splenic monocytes contribute to monocyte alterations after CBDL is unknown. This study evaluates monocyte distributions and assesses effects of splenectomy on monocyte levels and pulmonary vascular and hepatic abnormalities in experimental HPS. Methods Splenectomy was performed in CBDL animals. Monocyte levels in different tissues and circulation were assessed with CD68. Pulmonary alterations of HPS were evaluated with vascular endothelial growth factor‐A (VEGF‐A) levels, angiogenesis, and alveolar–arterial oxygen gradient (AaPO2). Liver abnormalities were evaluated with fibrosis (Sirius red), bile duct proliferation (CK‐19), and enzymatic changes. Results Monocyte levels increased in the lung and liver after CBDL and were accompanied by elevated circulating monocyte numbers. Splenectomy significantly decreased monocyte accumulation, VEGF‐A levels, and angiogenesis in CBDL animal lung and improved AaPO2 levels. In contrast, hepatic monocyte levels, fibrosis, and functional abnormalities were further exacerbated by spleen removal. Conclusions Splenic reservoir monocytes are a major source for lung monocyte accumulation after CBDL, and spleen removal attenuates the development of experimental HPS. Liver monocytes may have different origins, and accumulation is exacerbated after depletion of splenic reservoir monocytes. Tissue specific monocyte alterations, influenced by the spleen reservoir, have a significant impact on pulmonary complications of liver disease. PMID:27029414

[Scimitar syndrome. Correlation anatomo-embryological].

PubMed

Muñoz-Castellanos, Luis; Kuri-Nivon, Magdalena

2016-01-01

To describe morphologically a toracoabdominal visceral block of a scimitar's syndrome case. We propose a pathogenetic theory wich explains the development of the pulmonary venous connection in this syndrome. The anatomic specimen was described with the segmental sequential system. The situs was solitus, the connections between the cardiac segments and the associated anomalies were determined. The anatomy of both lungs, including the venous pulmonary connection, was described. A pathogenetic hypothesis was made, which explains the pulmonary venous connection throw a correlation between the pathology of this syndrome and the normal development of the pulmonary veins. The situs was solitus, the connections of the cardiac chambers were normal; there were hypoplasia and dysplasia of the right lung with sequestration of the inferior lobe; the right pulmonary veins were connected with a curved collector which drainaged into the suprahepatic segment of the inferior vena cava; the left pulmonary veins were open into the left atrium. The sequestered inferior lobe of the right lung received irrigation throw a collateral aortopulmonary vessel. There was an atrial septal defect. The pathogenetic hypothesis propose that the pulmonary venous connection in this syndrome represent the persistent of the Streeter's horizon xiv (28-30 days of development), period in which the sinus of the pulmonary veins has double connection, with the left atrium and with a primitive collector into the right viteline vein which forms the suprahepatic segment of the inferior vena cava. Copyright © 2015 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Differences in the effects of Asian dust on pulmonary function between adult patients with asthma and those with asthma–chronic obstructive pulmonary disease overlap syndrome

PubMed Central

Watanabe, Masanari; Noma, Hisashi; Kurai, Jun; Sano, Hiroyuki; Ueda, Yasuto; Mikami, Masaaki; Yamamoto, Hiroyuki; Tokuyasu, Hirokazu; Kato, Kazuhiro; Konishi, Tatsuya; Tatsukawa, Toshiyuki; Shimizu, Eiji; Kitano, Hiroya

2016-01-01

Background Asian dust (AD) exposure exacerbates pulmonary dysfunction in patients with asthma. Asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS), characterized by coexisting symptoms of asthma and chronic obstructive pulmonary disease, is considered a separate disease entity. Previously, we investigated the effects of AD on pulmonary function in adult patients with asthma. Here, we present the findings of our further research on the differences in the effects of AD exposure on pulmonary function between patients with asthma alone and those with ACOS. Methods Between March and May 2012, we conducted a panel study wherein we monitored daily peak expiratory flow (PEF) values in 231 adult patients with asthma. These patients were divided into 190 patients with asthma alone and 41 patients with ACOS in this study. Daily AD particle levels were measured using light detection and ranging systems. Two heavy AD days (April 23 and 24) were determined according to the Japan Meteorological Agency definition. A linear mixed model was used to estimate the association between PEF and AD exposure. Results Increments in the interquartile range of AD particles (0.018 km−1) led to PEF changes of −0.50 L/min (95% confidence interval, −0.98 to −0.02) in patients with asthma alone and −0.11 L/min (−0.11 to 0.85) in patients with ACOS. The PEF changes after exposure to heavy AD were −2.21 L/min (−4.28 to −0.15) in patients with asthma alone and −2.76 L/min (−6.86 to 1.35) in patients with ACOS. In patients with asthma alone, the highest decrease in PEF values was observed on the heavy AD day, with a subsequent gradual increase over time. Conclusion Our results suggest that the effects of AD exposure on pulmonary function differ between patients with asthma alone and ACOS, with the former exhibiting a greater likelihood of decreased pulmonary function after AD exposure. PMID:26869784

A rapid method for infectivity titration of Andes hantavirus using flow cytometry.

PubMed

Barriga, Gonzalo P; Martínez-Valdebenito, Constanza; Galeno, Héctor; Ferrés, Marcela; Lozach, Pierre-Yves; Tischler, Nicole D

2013-11-01

The focus assay is currently the most commonly used technique for hantavirus titer determination. This method requires an incubation time of between 5 and 11 days to allow the appearance of foci after several rounds of viral infection. The following work presents a rapid Andes virus (ANDV) titration assay, based on viral nucleocapsid protein (N) detection in infected cells by flow cytometry. To this end, an anti-N monoclonal antibody was used that was developed and characterized previously. ANDV N could be detected as early as 6 h post-infection, while viral release was not observed until 24-48 h post-infection. Given that ANDV detection was performed during its first round of infection, a time reduction for titer determination was possible and provided results in only two days. The viral titer was calculated from the percentage of N positive cells and agreed with focus assay titers. Furthermore, the assay was applied to quantify the inhibition of ANDV cell entry by patient sera and by preventing endosome acidification. This novel hantavirus titration assay is a highly quantitative and sensitive tool that facilitates infectivity titration of virus stocks, rapid screening for antiviral drugs, and may be further used to detect and quantify infectious virus in human samples. Copyright © 2013 Elsevier B.V. All rights reserved.

Effect of transjugular intrahepatic portosystemic shunt on pulmonary gas exchange in patients with portal hypertension and hepatopulmonary syndrome

PubMed Central

Martínez-Pallí, Graciela; Drake, Britt B; García-Pagán, Joan-Carles; Barberà, Joan-Albert; Arguedas, Miguel R; Rodriguez-Roisin, Robert; Bosch, Jaume; Fallon, Michael B

2005-01-01

AIM: To assess the impact of transjugular intrahepatic portosystemic shunt (TIPS) on pulmonary gas exchange and to evaluate the use of TIPS for the treatment of hepatopulmonary syndrome ( HPS ). METHODS: Seven patients, three of them with advanced HPS, in whom detailed pulmonary function tests were performed before and after TIPS placement at the University of Alabama Hospital and at the Hospital Clinic, Barcelona, were considered. RESULTS: TIPS patency was confirmed by hemodynamic evaluation. No changes in arterial blood gases were observed in the overall subset of patients. Transient arterial oxygenation improvement was observed in only one HPS patient, early after TIPS, but this was not sustained 4 mo later. CONCLUSION: TIPS neither improved nor worsened pulmonary gas exchange in patients with portal hypertension. This data does not support the use of TIPS as a specific treatment for HPS. However, it does reinforce the view that TIPS can be safely performed for the treatment of other complications of portal hypertension in patients with HPS. PMID:16425397

Lung-Protective Ventilation With Low Tidal Volumes and the Occurrence of Pulmonary Complications in Patients Without Acute Respiratory Distress Syndrome: A Systematic Review and Individual Patient Data Analysis.

PubMed

Neto, Ary Serpa; Simonis, Fabienne D; Barbas, Carmen S V; Biehl, Michelle; Determann, Rogier M; Elmer, Jonathan; Friedman, Gilberto; Gajic, Ognjen; Goldstein, Joshua N; Linko, Rita; Pinheiro de Oliveira, Roselaine; Sundar, Sugantha; Talmor, Daniel; Wolthuis, Esther K; Gama de Abreu, Marcelo; Pelosi, Paolo; Schultz, Marcus J

2015-10-01

Protective mechanical ventilation with low tidal volumes is standard of care for patients with acute respiratory distress syndrome. The aim of this individual patient data analysis was to determine the association between tidal volume and the occurrence of pulmonary complications in ICU patients without acute respiratory distress syndrome and the association between occurrence of pulmonary complications and outcome in these patients. Individual patient data analysis. ICU patients not fulfilling the consensus criteria for acute respiratory distress syndrome at the onset of ventilation. Mechanical ventilation with low tidal volume. The primary endpoint was development of a composite of acute respiratory distress syndrome and pneumonia during hospital stay. Based on the tertiles of tidal volume size in the first 2 days of ventilation, patients were assigned to a "low tidal volume group" (tidal volumes ≤ 7 mL/kg predicted body weight), an "intermediate tidal volume group" (> 7 and < 10 mL/kg predicted body weight), and a "high tidal volume group" (≥ 10 mL/kg predicted body weight). Seven investigations (2,184 patients) were included. Acute respiratory distress syndrome or pneumonia occurred in 23% of patients in the low tidal volume group, in 28% of patients in the intermediate tidal volume group, and in 31% of the patients in the high tidal volume group (adjusted odds ratio [low vs high tidal volume group], 0.72; 95% CI, 0.52-0.98; p = 0.042). Occurrence of pulmonary complications was associated with a lower number of ICU-free and hospital-free days and alive at day 28 (10.0 ± 10.9 vs 13.8 ± 11.6 d; p < 0.01 and 6.1 ± 8.1 vs 8.9 ± 9.4 d; p < 0.01) and an increased hospital mortality (49.5% vs 35.6%; p < 0.01). Ventilation with low tidal volumes is associated with a lower risk of development of pulmonary complications in patients without acute respiratory distress syndrome.

Prevention and treatment of the post-thrombotic syndrome and of the chronic thromboembolic pulmonary hypertension.

PubMed

Pesavento, Raffaele; Prandoni, Paolo

2015-02-01

Post-thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (CTEPH) are late complications of venous thromboembolism. The purpose of this review is to present and discuss recently published studies that have improved our knowledge of PTS and CTEPH. The current understanding of the pathophysiology of PTS and CTEPH is discussed as well as the importance of chronic residual venous thrombosis, some polymorphisms of plasminogen activator inhibitor-1, and the current concept of misguided thrombus resolution. The surprising finding that elastic compression stockings may not be effective in preventing PTS and the novel medical treatment in CTEPH are discussed in detail. Novel direct oral anticoagulants show potential for prevention of PTS. No firm conclusions can be drawn on the efficacy of elastic stockings. Novel treatments of CTEPH for inoperable patients and those with persistent pulmonary hypertension after surgery have become available and further research on wider indication for their use is urgently needed.

Isolation of sochi virus from a fatal case of hantavirus disease with fulminant clinical course.

PubMed

Dzagurova, Tamara K; Witkowski, Peter T; Tkachenko, Evgeniy A; Klempa, Boris; Morozov, Vyacheslav G; Auste, Brita; Zavora, Dmitriy L; Iunicheva, Iulia V; Mutnih, Elena S; Kruger, Detlev H

2012-01-01

Sochi virus, a novel genetic variant of Dobrava-Belgrade virus, was isolated in cell culture from a fulminant lethal case of hantavirus disease presenting with shock and combined kidney and lung failure. Sochi virus is transmitted to humans from host reservoir Apodemus ponticus and must be considered a life-threatening emerging agent.

Acoustic evaluation of pirfenidone on patients with combined pulmonary fibrosis emphysema syndrome.

PubMed

Charleston-Villalobos, Sonia; Castaneda-Villa, Norma; Gonzalez-Camarena, Ramon; Mejia-Avila, M; Mateos-Toledo, H; Aljama-Corrales, Tomas

2016-08-01

The combined pulmonary fibrosis emphysema syndrome (CPFES) overall has a poor prognosis with a 5-year survival of 35-80%. Consequently, to evaluate possible positive effects on patients of novel agents as pirfenidone is relevant. However, the efficacy of pirfenidone in CPFES patients is still not well-known. In this study we propose an alternative to evaluate the effects of pirfenidone treatment on CPFES patients via acoustic information. Quantitative analysis of discontinuous adventitious lung sounds (DLS), known as crackles, has been promising to detect and characterize diverse pulmonary pathologies. The present study combines independent components (ICs) analysis of LS and the automated selection of ICs associated with DLS. ICs's features as fractal dimension, entropy and sparsity produce several clusters by kmeans. Those clusters containing ICs of DLS are exclusively considered to finally estimate the number of DLS per ICs by a time-variant AR modeling. For the evaluation of the effects of pirfenidone, the 2D DLS-ICs spatial distribution in conjunction with the estimated number of DLS events are shown. The methodology is applied to two real cases of CPFES with 6 and 12 months of treatment. The acoustical evaluation indicates that pirfenidone treatment may not be satisfactory for CPFES patients but further evaluation has to be performed.

Hantaan virus nucleocapsid protein binds to importin alpha proteins and inhibits tumor necrosis factor alpha-induced activation of nuclear factor kappa B.

PubMed

Taylor, Shannon L; Frias-Staheli, Natalia; García-Sastre, Adolfo; Schmaljohn, Connie S

2009-02-01

Hantaviruses such as Hantaan virus (HTNV) and Andes virus cause two human diseases, hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome, respectively. For both, disease pathogenesis is thought to be immunologically mediated and there have been numerous reports of patients with elevated levels of proinflammatory and inflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha), in their sera. Multiple viruses have developed evasion strategies to circumvent the host cell inflammatory process, with one of the most prevalent being the disruption of nuclear factor kappa B (NF-kappaB) activation. We hypothesized that hantaviruses might also moderate host inflammation by interfering with this pathway. We report here that the nucleocapsid (N) protein of HTNV was able to inhibit TNF-alpha-induced activation of NF-kappaB, as measured by a reporter assay, and the activation of endogenous p65, an NF-kappaB subunit. Surprisingly, there was no defect in the degradation of the inhibitor of NF-kappaB (IkappaB) protein, nor was there any alteration in the level of p65 expression in HTNV N-expressing cells. However, immunofluorescence antibody staining demonstrated that cells expressing HTNV N protein and a green fluorescent protein-p65 fusion had limited p65 nuclear translocation. Furthermore, we were able to detect an interaction between HTNV N protein and importin alpha, a nuclear import molecule responsible for shuttling NF-kappaB to the nucleus. Collectively, our data suggest that HTNV N protein can sequester NF-kappaB in the cytoplasm, thus inhibiting NF-kappaB activity. These findings, which were obtained using cells transfected with cDNA representing the HTNV N gene, were confirmed using HTNV-infected cells.

Adenoviral transfer of HSP-70 into pulmonary epithelium ameliorates experimental acute respiratory distress syndrome.

PubMed

Weiss, Yoram G; Maloyan, Alina; Tazelaar, John; Raj, Nichelle; Deutschman, Clifford S

2002-09-01

The acute respiratory distress syndrome (ARDS) provokes three pathologic processes: unchecked inflammation, interstitial/alveolar protein accumulation, and destruction of pulmonary epithelial cells. The highly conserved heat shock protein HSP-70 can limit all three responses but is not appropriately expressed in the lungs after cecal ligation and double puncture (2CLP), a clinically relevant model of ARDS. We hypothesize that restoring expression of HSP-70 using adenovirus-mediated gene therapy will limit pulmonary pathology following 2CLP. We administered a vector containing the porcine HSP-70 cDNA driven by a CMV promoter (AdHSP) into the lungs of rats subjected to 2CLP or sham operation. Administration of AdHSP after either sham operation or 2CLP increased HSP-70 protein expression in lung tissue, as determined by immunohistochemistry and Western blot hybridization. Administration of AdHSP significantly attenuated interstitial and alveolar edema and protein exudation and dramatically decreased neutrophil accumulation, relative to a control adenovirus. CLP-associated mortality at 48 hours was reduced by half. Modulation of HSP-70 production reduces pathologic changes and may improve outcome in experimental ARDS.

Plagues in the ICU: a brief history of community-acquired epidemic and endemic transmissible infections leading to intensive care admission.

PubMed

Light, R Bruce

2009-01-01

The ability to diagnose and treat infectious diseases and handle infectious disease outbreaks continues to improve. For the most part, the major plagues of antiquity remain historical footnotes, yet, despite many advances, there is clear evidence that major pandemic illness is always just one outbreak away. In addition to the HIV pandemic, the smaller epidemic outbreaks of Legionnaire's disease, hantavirus pulmonary syndrome, and severe acute respiratory syndrome, among many others, points out the potential risk associated with a lack of preplanning and preparedness. Although pandemic influenza is at the top of the list when discussing possible future major infectious disease outbreaks, the truth is that the identity of the next major pandemic pathogen cannot be predicted with any accuracy. We can only hope that general preparedness and the lessons learned from previous outbreaks suffice.

Pulmonary Hypertension in Congenital Heart Disease: Beyond Eisenmenger Syndrome.

PubMed

Krieger, Eric V; Leary, Peter J; Opotowsky, Alexander R

2015-11-01

Patients with adult congenital heart disease have an increased risk of developing pulmonary hypertension. There are several mechanisms of pulmonary hypertension in patients with adult congenital heart disease, and understanding them requires a systematic approach to define the patient's hemodynamics and physiology. This article reviews the updated classification of pulmonary hypertension in patients with adult congenital heart disease with a focus on pathophysiology, diagnostics, and the evaluation of pulmonary hypertension in special adult congenital heart disease populations. Copyright © 2015 Elsevier Inc. All rights reserved.

Vascular Ehlers–Danlos syndrome with cryptorchidism, recurrent pneumothorax, and pulmonary capillary hemangiomatosis-like foci

PubMed Central

Park, Min A.; Shin, So Youn; Kim, Young Jin; Park, Myung Jae; Lee, Seung Hyeun

2017-01-01

Abstract Rationale: Vascular Ehlers–Danlos syndrome (vEDS) is a rare autosomal dominant inherited collagen disorder caused by defects or deficiency of pro-alpha 1 chain of type III procollagen encoded by COL3A1. vEDS is characterized not only by soft tissue manifestations including hyperextensibility of skin and joint hypermobility but also by early mortality due to rupture of arteries or vital organs. Although pulmonary complications are not common, vEDS cases complicated by pneumothorax, hemothorax, or intrapulmonary hematoma have been reported. When a patient initially presents only with pulmonary complications, it is not easy for clinicians to suspect vEDS. Patient concerns: We report a case of an 18-year-old high school student, with a past history of cryptorchidism, presenting with recurrent pneumothorax. Diagnoses: Routine laboratory findings were unremarkable. Chest high resolution computed tomographic scan showed age-unmatched hyperinflation of both lungs, atypical cystic changes and multifocal ground glass opacities scattered in both lower lobes. His slender body shape, hyperflexible joints, and hyperextensible skin provided clue to suspicion of a possible connective tissue disorder. Interventions: The histological examination of the lung lesions showed excessive capillary proliferation in the pulmonary interstitium and pleura allowing the diagnosis of pulmonary capillary hemangiomatosis (PCH)-like foci. Genetic study revealed COL3A1 gene splicing site mutation confirming his diagnosis as vEDS. Outcomes: Although his diagnosis vEDS is notorious for fatal vascular complication, there was no evidence of such complication at presentation. Fortunately, he has been followed up for 10 months without pulmonary or vascular complications. Lessons: To the best of our knowledge, both cryptorchidism and PCH-like foci have never been reported yet as complications of vEDS, suggesting our case might be a new variant of this condition. This case emphasizes the

Medical utilization and cost in patients with overlap syndrome of chronic obstructive pulmonary disease and asthma.

PubMed

Rhee, Chin Kook; Yoon, Hyoung Kyu; Yoo, Kwang Ha; Kim, Young Sam; Lee, Sei Won; Park, Yong Bum; Lee, Jin Hwa; Kim, Yuri; Kim, Kyungjoo; Kim, Jinhee; Oh, Yeon Mok; Lee, Sang Do

2014-04-01

Little information is available regarding medical utilization and cost in patients with overlap syndrome of chronic obstructive pulmonary disease (COPD) and asthma. The purpose of this study is to analyze medical utilization and cost in patients with overlap syndrome and to compare them to COPD patients without asthma. Using the 2009 Korean National Health Insurance (NHI) database, COPD patients were identified. Medical utilization and costs were also analyzed. Of a total of 185,147 patients identified with COPD, 101,004 patients were classified with overlap syndrome of COPD and asthma and 84,143 patients with COPD without asthma. In 2009, the percentages of emergency room visits, admissions, and intensive care unit admissions were 14.6%, 30.5%, and 0.5%, respectively, in the patients with overlap syndrome group and 5.0%, 14.1%, and 0.2%, respectively, in the COPD patients without asthma group (p < 0.05 for all comparisons). The cost of medical utilization was 790 ± 71 US dollars per person and 3,373 ± 4,628 dollars per person for outpatient and inpatient services, respectively, in the patients with overlap syndrome and 413 ± 512 and 3,010 ± 5,013, respectively, in the COPD patients without asthma (p < 0.05 for all comparisons). Multiple linear regression showed that age, sex, overlap syndrome, hospitalization in the last year, low socioeconomic status, and type of hospital use were significant factors affecting medical utilization and cost. In patients with overlap syndrome, both medical utilization and cost were higher than in COPD patients without asthma.

Animal Models for the Study of Rodent-Borne Hemorrhagic Fever Viruses: Arenaviruses and Hantaviruses

PubMed Central

Golden, Joseph W.; Hammerbeck, Christopher D.; Mucker, Eric M.; Brocato, Rebecca L.

2015-01-01

Human pathogenic hantaviruses and arenaviruses are maintained in nature by persistent infection of rodent carrier populations. Several members of these virus groups can cause significant disease in humans that is generically termed viral hemorrhagic fever (HF) and is characterized as a febrile illness with an increased propensity to cause acute inflammation. Human interaction with rodent carrier populations leads to infection. Arenaviruses are also viewed as potential biological weapons threat agents. There is an increased interest in studying these viruses in animal models to gain a deeper understating not only of viral pathogenesis, but also for the evaluation of medical countermeasures (MCM) to mitigate disease threats. In this review, we examine current knowledge regarding animal models employed in the study of these viruses. We include analysis of infection models in natural reservoirs and also discuss the impact of strain heterogeneity on the susceptibility of animals to infection. This information should provide a comprehensive reference for those interested in the study of arenaviruses and hantaviruses not only for MCM development but also in the study of viral pathogenesis and the biology of these viruses in their natural reservoirs. PMID:26266264

Fat embolism syndrome

PubMed Central

Richards, Robin R.

1997-01-01

Fat embolism syndrome, an important contributor to the development of acute respiratory distress syndrome, has been associated with both traumatic and nontraumatic disorders. Fat embolization after long bone trauma is probably common as a subclinical event. Fat emboli can deform and pass through the lungs, resulting in systemic embolization, most commonly to the brain and kidneys. The diagnosis of fat embolism syndrome is based on the patient’s history, supported by clinical signs of pulmonary, cerebral and cutaneous dysfunction and confirmed by the demonstration of arterial hypoxemia in the absence of other disorders. Treatment of fat embolism syndrome consists of general supportive measures, including splinting, maintenance of fluid and electrolyte balance and the administration of oxygen. Endotracheal intubation and mechanical ventilatory assistance can be indicated. The role of corticosteroids remains controversial. Early stabilization of long bone fractures has been shown to decrease the incidence of pulmonary complications. Clinical and experimental studies suggest that the exact method of fracture fixation plays a minor role in the development of pulmonary dysfunction. As more is learned about the specifics of the various triggers for the development of fat embolism syndrome, it is hoped that the prospect of more specific therapy for the prevention and treatment of this disorder will become a reality. PMID:9336522

Pulmonary Neoplasms in Patients with Birt-Hogg-Dubé Syndrome: Histopathological Features and Genetic and Somatic Events.

PubMed

Furuya, Mitsuko; Tanaka, Reiko; Okudela, Koji; Nakamura, Satoko; Yoshioka, Hiromu; Tsuzuki, Toyonori; Shibuya, Ryo; Yatera, Kazuhiro; Shirasaki, Hiroki; Sudo, Yoshiko; Kimura, Naoko; Yamada, Kazuaki; Uematsu, Shugo; Kunimura, Toshiaki; Kato, Ikuma; Nakatani, Yukio

2016-01-01

Birt-Hogg-Dubé syndrome (BHD) is an inherited disorder caused by genetic mutations in the folliculin (FLCN) gene. Individuals with BHD have multiple pulmonary cysts and are at a high risk for developing renal cell carcinomas (RCCs). Currently, little information is available about whether pulmonary cysts are absolutely benign or if the lungs are at an increased risk for developing neoplasms. Herein, we describe 14 pulmonary neoplastic lesions in 7 patients with BHD. All patients were confirmed to have germline FLCN mutations. Neoplasm histologies included adenocarcinoma in situ (n = 2), minimally invasive adenocarcinoma (n = 1), papillary adenocarcinoma (n = 1), micropapillary adenocarcinoma (n = 1), atypical adenomatous hyperplasia (n = 8), and micronodular pneumocyte hyperplasia (MPH)-like lesion (n = 1). Five of the six adenocarcinoma/MPH-like lesions (83.3%) demonstrated a loss of heterozygosity (LOH) of FLCN. All of these lesions lacked mutant alleles and preserved wild-type alleles. Three invasive adenocarcinomas possessed additional somatic events: 2 had a somatic mutation in the epidermal growth factor receptor gene (EGFR) and another had a somatic mutation in KRAS. Immunohistochemical analysis revealed that most of the lesions were immunostained for phospho-mammalian target of rapamycin (p-mTOR) and phospho-S6. Collective data indicated that pulmonary neoplasms of peripheral adenocarcinomatous lineage in BHD patients frequently exhibit LOH of FLCN with mTOR pathway signaling. Additional driver gene mutations were detected only in invasive cases, suggesting that FLCN LOH may be an underlying abnormality that cooperates with major driver gene mutations in the progression of pulmonary adenocarcinomas in BHD patients.

Dysregulated expression of microRNAs and mRNAs in pulmonary artery remodeling in ascites syndrome in broiler chickens

PubMed Central

Zhuang, Yu; Xiao, Qingyang; Cao, Huabin; Zhang, Caiying; Wang, Tiancheng; Lin, Huayuan; Guo, Xiaoquan; Hu, Guoliang

2017-01-01

Ascites syndrome (AS), also known as pulmonary artery hypertension, remains a challenging disease that severely affects both humans and broiler chickens. Pulmonary artery remodeling presents a key step in the development of AS. In this study, we obtained pulmonary artery tissues from broilers with and without AS to perform miRNA sequencing analysis, miRNA-mRNA association analysis and pathological examinations. 29 significantly differentially expressed miRNAs were found both in known and novel miRNAs with 18 up-regulated and 11 down-regulated miRNAs. Their predicted potential targets were involved in a wide range of functional clusters as indicated via GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses. The upregulation of miR-155, miR-23b-3p, miR-146b-5p and miR-146b-3p were found closely associated with the pathogenesis of pulmonary artery remodeling in AS progression. The association analysis for the miRNAs-mRNAs showed that these 29 significantly differentially expressed miRNAs regulate 162 differentially expressed target genes. Among them, 20 miRNAs correlated with 18 predicted target genes that appear to be involved in pulmonary artery remodeling, mainly in three broad physiological processes: the hypoxia sensing response (HIF1a, NHE1, STAT5 and STAT3), endothelial permeability dysfunction (CD44, TRAF2, CDK2AP1, LZTFL1, JAZF1, PEBP1, LRP1B, RPS14 and THBS2) and inflammation (MEOX2, STAT5, STAT3, IRF8, MAP3K8, IL-1BETA and TNFRSF1B). Pathological pulmonary artery remodeling in the AS broilers was consistently observed in the present study. Taken together, the current analysis further illuminates the molecular mechanism of pulmonary artery remodeling underlying AS progression. PMID:27791988

Pulmonary complications of cirrhosis.

PubMed

Singh, C; Sager, J S

2009-07-01

Advanced liver disease and portal hypertension produce various intrathoracic complications that involve the pleural space, the lung parenchyma, and the pulmonary circulation. Dyspnea and arterial hypoxemia are the most common symptoms and signs in patients with such complications. This article focuses on the diagnosis and management of hepatopulmonary syndrome, portopulmonary hypertension, and hepatic hydrothorax. All are pulmonary processes associated with end-stage liver disease that lead to significant morbidity and affect the quality of life of patients who are suffering from liver cirrhosis.

Pathologic aneurysmal dilation of the ascending aorta and dilation of the main pulmonary artery in patients with Kabuki syndrome: valve-sparing aortic root replacement.

PubMed

Dyamenahalli, Umesh; Abraham, Boban; Fontenot, Eudice; Prasad, Vinay; Imamura, Michiaki

2007-01-01

We report the aneurysmal dilation of the ascending aorta and the main pulmonary artery in 2 children with Kabuki syndrome. In 1 patient, there was progressive aneurysmal dilation of the ascending aorta necessitating aortoplasty. Histologic examination of the resected aorta revealed disrupted and fragmented elastic fibers in the medial layer, along with mucinous degeneration of the aortic wall. This is the first recognition and report of these findings as part of the Kabuki syndrome.

Shrinking lung syndrome as a manifestation of pleuritis: a new model based on pulmonary physiological studies.

PubMed

Henderson, Lauren A; Loring, Stephen H; Gill, Ritu R; Liao, Katherine P; Ishizawar, Rumey; Kim, Susan; Perlmutter-Goldenson, Robin; Rothman, Deborah; Son, Mary Beth F; Stoll, Matthew L; Zemel, Lawrence S; Sandborg, Christy; Dellaripa, Paul F; Nigrovic, Peter A

2013-03-01

The pathophysiology of shrinking lung syndrome (SLS) is poorly understood. We sought to define the structural basis for this condition through the study of pulmonary mechanics in affected patients. Since 2007, most patients evaluated for SLS at our institutions have undergone standardized respiratory testing including esophageal manometry. We analyzed these studies to define the physiological abnormalities driving respiratory restriction. Chest computed tomography data were post-processed to quantify lung volume and parenchymal density. Six cases met criteria for SLS. All presented with dyspnea as well as pleurisy and/or transient pleural effusions. Chest imaging results were free of parenchymal disease and corrected diffusing capacities were normal. Total lung capacities were 39%-50% of predicted. Maximal inspiratory pressures were impaired at high lung volumes, but not low lung volumes, in 5 patients. Lung compliance was strikingly reduced in all patients, accompanied by increased parenchymal density. Patients with SLS exhibited symptomatic and/or radiographic pleuritis associated with 2 characteristic physiological abnormalities: (1) impaired respiratory force at high but not low lung volumes; and (2) markedly decreased pulmonary compliance in the absence of identifiable interstitial lung disease. These findings suggest a model in which pleural inflammation chronically impairs deep inspiration, for example through neural reflexes, leading to parenchymal reorganization that impairs lung compliance, a known complication of persistently low lung volumes. Together these processes could account for the association of SLS with pleuritis as well as the gradual symptomatic and functional progression that is a hallmark of this syndrome.

[Pulmonary complications of malaria: An update].

PubMed

Cabezón Estévanez, Itxasne; Górgolas Hernández-Mora, Miguel

2016-04-15

Malaria is the most important parasitic disease worldwide, being a public health challenge in more than 90 countries. The incidence of pulmonary manifestations has increased in recent years. Acute respiratory distress syndrome is the most severe form within the pulmonary complications of malaria, with high mortality despite proper management. This syndrome manifests with sudden dyspnoea, cough and refractory hypoxaemia. Patients should be admitted to intensive care units and treated with parenteral antimalarial drug treatment and ventilatory and haemodynamic support without delay. Therefore, dyspnoea in patients with malaria should alert clinicians, as the development of respiratory distress is a poor prognostic factor. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Anomalous origin of circumflex coronary artery from right pulmonary artery in a hypoplastic left heart syndrome child

PubMed Central

Kansy, Andrzej; Łaniewski-Wołłk, Przemysław

2014-01-01

We describe the case of a newborn with hypoplastic left heart syndrome (HLHS) and aberrant origin of the circumflex coronary artery from the right pulmonary artery. The patient underwent a modified Norwood procedure with direct reimplantation of the circumflex coronary artery to the neo-aorta, but died on the 5th postoperative day because of myocardial failure. Detailed assessment of coronary arteries as part of the routine echocardiographic evaluation of HLHS and intraoperative inspection of them is crucial. PMID:26336423

[Surgical repair of Scimitar syndrome with azygos connection by extracardiac conduit between right pulmonary vein and left atrium].

PubMed

Noji, S; Kitamura, N; Yamaguchi, A; Otaki, M; Miki, T; Tamura, H

1991-08-01

We present a surgical case of 41-year-old woman with Scimitar syndrome. Preoperative catheterization showed azygos connection and L-R shunt ratio of 45% without intracardiac malformations. To our knowledge, this combination has not been previously reported. At operation the right single pulmonary vein was found and drained into the inferior vena cava below the diaphragm. Because of counter clockwise rotation of the heart the distance of the scimitar vein and the left atrium was too long for direct anastomosis, a polytetrafluoroethylene tube (10 mm in diameter) was utilized for an extracardiac conduit using cardiopulmonary bypass. Postoperative course was uneventful. We conclude that this technique is effective for this syndrome with a large amount of L-R shunt and a sufficient patency is expected.

Hantavirus Gc induces long-term immune protection via LAMP-targeting DNA vaccine strategy.

PubMed

Jiang, Dong-Bo; Zhang, Jin-Peng; Cheng, Lin-Feng; Zhang, Guan-Wen; Li, Yun; Li, Zi-Chao; Lu, Zhen-Hua; Zhang, Zi-Xin; Lu, Yu-Chen; Zheng, Lian-He; Zhang, Fang-Lin; Yang, Kun

2018-02-01

Hemorrhagic fever with renal syndrome (HFRS) occurs widely throughout Eurasia. Unfortunately, there is no effective treatment, and prophylaxis remains the best option against the major pathogenic agent, hantaan virus (HTNV), which is an Old World hantavirus. However, the absence of cellular immune responses and immunological memory hampers acceptance of the current inactivated HFRS vaccine. Previous studies revealed that a lysosome-associated membrane protein 1 (LAMP1)-targeting strategy involving a DNA vaccine based on the HTNV glycoprotein Gn successfully conferred long-term immunity, and indicated that further research on Gc, another HTNV antigen, was warranted. Plasmids encoding Gc and lysosome-targeted Gc, designated pVAX-Gc and pVAX-LAMP/Gc, respectively, were constructed. Proteins of interest were identified by fluorescence microscopy following cell line transfection. Five groups of 20 female BALB/c mice were subjected to the following inoculations: inactivated HTNV vaccine, pVAX-LAMP/Gc, pVAX-Gc, and, as the negative controls, pVAX-LAMP or the blank vector pVAX1. Humoral and cellular immunity were assessed by enzyme-linked immunosorbent assays (ELISAs) and 15-mer peptide enzyme-linked immunospot (ELISpot) epitope mapping assays. Repeated immunization with pVAX-LAMP/Gc enhanced adaptive immune responses, as demonstrated by the specific and neutralizing antibody titers and increased IFN-γ production. The inactivated vaccine induced a comparable humoral reaction, but the negative controls only elicited insignificant responses. Using a mouse model of HTNV challenge, the in vivo protection conferred by the inactivated vaccine and Gc-based constructs (with/without LAMP recombination) was confirmed. Evidence of pan-epitope reactions highlighted the long-term cellular response to the LAMP-targeting strategy, and histological observations indicated the safety of the LAMP-targeting vaccines. The long-term protective immune responses induced by pVAX-LAMP/Gc may be

Diagnostic delay of pulmonary tuberculosis in patients with acute respiratory distress syndrome associated with aspiration pneumonia: Two case reports and a mini-review from Japan

PubMed Central

Nakao, Makoto; Sone, Kazuki; Kagawa, Yusuke; Kurokawa, Ryota; Sato, Hidefumi; Kunieda, Takefumi; Muramatsu, Hideki

2016-01-01

Diagnosing active tuberculosis in elderly patients presents problems due to nonspecific symptoms and complications such as aspiration pneumonia. The current study presents two cases of pulmonary tuberculosis with bilateral pulmonary infiltrates associated with aspiration pneumonia. The two elderly patients developed acute respiratory distress syndrome as a result of aspiration pneumonia. The diagnoses of pulmonary tuberculosis were delayed in both cases, as the patients were diagnosed with active tuberculosis following discharge from hospital. The sputum test for acid-fast bacillus at the time of administration was smear-negative/culture-positive in these patients. They were treated with isoniazid, rifampicin and ethambutol, and nosocomial transmission of tuberculosis from these patients was not reported. The number of elderly patients with aspiration pneumonia is predicted to increase rapidly, and aspiration pneumonia combined with pulmonary tuberculosis is a major medical and healthcare concern in Japan. The present study concludes that physicians should always consider the complication of pulmonary tuberculosis when treating pneumonia patients, in particular in treating elderly patients with pulmonary infiltrates. PMID:27446284

Williams-Beuren's Syndrome: A Case Report.

PubMed

Zamani, Hassan; Babazadeh, Kazem; Fattahi, Saeid; Mokhtari-Esbuie, Farzad

2012-01-01

Williams-Beuren syndrome is a rare familial multisystem disorder occurring in 1 per 20,000 live births. It is characterized by congenital heart defects (CHD), skeletal and renal anomalies, cognitive disorder, social personality disorder and dysmorphic facies. We present a case of Williams syndrome that presented to us with heart murmur and cognitive problem. A 5-year-old girl referred to pediatric cardiologist because of heart murmurs. She had a systolic murmur (2-3/6) in right upper sternal border with radiation to right cervical region. She also had a bulge forehead. Angiography showed mild supra valvular aortic stenosis and mild multiple peripheral pulmonary stenosis. Fluorescent in situ hybridization (FISH) was performed and the result was: 46.XX, ish del (7q11.2) (ELN X1) (7q22 X2) ELN deletion compatible with Williams syndrome. Peripheral pulmonary artery stenosis is associated with Noonan syndrome, Alagille syndrome, Cutis laxa, Ehler-Danlos syndrome, and Silver-Russel syndrome. The patient had peripheral pulmonary artery stenosis, but no other signs of these syndromes were present, and also she had a supravalvular aortic stenosis which was not seen in other syndromes except Williams syndrome. Conclusion. According to primary symptoms, paraclinical and clinical finding such as dysmorphic facies, cognitive disorder and congenital heart defect, Williams syndrome was the first diagnosis. We suggest a more attention for evaluating heart murmur in childhood period, especially when the patient has abnormal facial features or mental problem.

Williams-Beuren's Syndrome: A Case Report

PubMed Central

Zamani, Hassan; Babazadeh, Kazem; Fattahi, Saeid; Mokhtari-Esbuie, Farzad

2012-01-01

Williams-Beuren syndrome is a rare familial multisystem disorder occurring in 1 per 20,000 live births. It is characterized by congenital heart defects (CHD), skeletal and renal anomalies, cognitive disorder, social personality disorder and dysmorphic facies. We present a case of Williams syndrome that presented to us with heart murmur and cognitive problem. A 5-year-old girl referred to pediatric cardiologist because of heart murmurs. She had a systolic murmur (2-3/6) in right upper sternal border with radiation to right cervical region. She also had a bulge forehead. Angiography showed mild supra valvular aortic stenosis and mild multiple peripheral pulmonary stenosis. Fluorescent in situ hybridization (FISH) was performed and the result was: 46.XX, ish del (7q11.2) (ELN X1) (7q22 X2) ELN deletion compatible with Williams syndrome. Peripheral pulmonary artery stenosis is associated with Noonan syndrome, Alagille syndrome, Cutis laxa, Ehler-Danlos syndrome, and Silver-Russel syndrome. The patient had peripheral pulmonary artery stenosis, but no other signs of these syndromes were present, and also she had a supravalvular aortic stenosis which was not seen in other syndromes except Williams syndrome. Conclusion. According to primary symptoms, paraclinical and clinical finding such as dysmorphic facies, cognitive disorder and congenital heart defect, Williams syndrome was the first diagnosis. We suggest a more attention for evaluating heart murmur in childhood period, especially when the patient has abnormal facial features or mental problem. PMID:22927862

Pulmonary Vascular Complications of Liver Disease

PubMed Central

Fritz, Jason S.; Fallon, Michael B.

2013-01-01

Hepatopulmonary syndrome and portopulmonary hypertension are two pulmonary vascular complications of liver disease. The pathophysiology underlying each disorder is distinct, but patients with either condition may be limited by dyspnea. A careful evaluation of concomitant symptoms, the physical examination, pulmonary function testing and arterial blood gas analysis, and echocardiographic, imaging, and hemodynamic studies is crucial to establishing (and distinguishing) these diagnoses. Our understanding of the pathobiology, natural history, and treatment of these disorders has advanced considerably over the past decade; however, the presence of either still increases the risk of morbidity and mortality in patients with underlying liver disease. There is no effective medical treatment for hepatopulmonary syndrome. Although liver transplantation can resolve hepatopulmonary syndrome, there appears to be worse survival even with transplantation. Liver transplantation poses a very high risk of death in those with significant portopulmonary hypertension, where targeted medical therapies may improve functional status and allow successful transplantation in a small number of select patients. PMID:23155142

Pulmonary eosinophilia associated with montelukast

PubMed Central

Franco, J.; Artes, M. J.

1999-01-01

Antileukotriene drugs are new therapeutic agents that have recently been approved for the treatment of asthma. Several cases of eosinophilic conditions including Churg-Strauss syndrome have been reported to be associated with zafirlukast, a cysteinyl leukotriene type 1 receptor antagonist. So far no other leukotriene modifier has been associated with the syndrome. The case history is presented of a man with allergic rhinitis and asthma who had received intermittent pulse therapy with oral corticosteroids. Pulmonary eosinophilia developed while he was receiving treatment with montelukast, a chemically distinct cysteinyl leukotriene type 1 receptor antagonist. After discontinuation of montelukast therapy and administration of systemic corticosteroids the patient's symptoms reversed rapidly and there was prompt resolution of the pulmonary infiltrates. We believe that cysteinyl leukotriene type 1 receptor antagonists are safe and effective drugs for most patients with asthma but caution is needed for those with more severe disease who require systemic corticosteroids, especially if they show characteristics of the atypical allergic diathesis seen in the prodromal phase of Churg-Strauss syndrome.

 PMID:10335014

Tula hantavirus L protein is a 250 kDa perinuclear membrane-associated protein.

PubMed

Kukkonen, Sami K J; Vaheri, Antti; Plyusnin, Alexander

2004-05-01

The complete open reading frame of Tula hantavirus (TULV) L RNA was cloned in three parts. The middle third (nt 2191-4344) could be expressed in E. coli and was used to immunize rabbits. The resultant antiserum was then used to immunoblot concentrated TULV and infected Vero E6 cells. The L protein of a hantavirus was detected, for the first time, in infected cells and was found to be expressed as a single protein with an apparent molecular mass of 250 kDa in both virions and infected cells. Using the antiserum, the expression level of the L protein was followed and image analysis of immunoblots indicated that there were 10(4) copies per cell at the peak level of expression. The antiserum was also used to detect the L protein in cell fractionation studies. In cells infected with TULV and cells expressing recombinant L, the protein pelleted with the microsomal membrane fraction. The membrane association was confirmed with membrane flotation assays. To visualize L protein localization in cells, a fusion protein of L and enhanced green fluorescent protein, L-EGFP, was expressed in Vero E6 cells with a plasmid-driven T7 expression system. L-EGFP localized in the perinuclear region where it had partial co-localization with the Golgi matrix protein GM130 and the TULV nucleocapsid protein.

Viral hemorrhagic fever cases in the country of Georgia: Acute Febrile Illness Surveillance Study results.

PubMed

Kuchuloria, Tinatin; Imnadze, Paata; Chokheli, Maiko; Tsertsvadze, Tengiz; Endeladze, Marina; Mshvidobadze, Ketevan; Clark, Danielle V; Bautista, Christian T; Abdel Fadeel, Moustafa; Pimentel, Guillermo; House, Brent; Hepburn, Matthew J; Wölfel, Silke; Wölfel, Roman; Rivard, Robert G

2014-08-01

Minimal information is available on the incidence of Crimean-Congo hemorrhagic fever (CCHF) virus and hantavirus infections in Georgia. From 2008 to 2011, 537 patients with fever ≥ 38°C for ≥ 48 hours without a diagnosis were enrolled into a sentinel surveillance study to investigate the incidence of nine pathogens, including CCHF virus and hantavirus. Of 14 patients with a hemorrhagic fever syndrome, 3 patients tested positive for CCHF virus immunoglobulin M (IgM) antibodies. Two of the patients enrolled in the study had acute renal failure. These 2 of 537 enrolled patients were the only patients in the study positive for hantavirus IgM antibodies. These results suggest that CCHF virus and hantavirus are contributing causes of acute febrile syndromes of infectious origin in Georgia. These findings support introduction of critical diagnostic approaches and confirm the need for additional surveillance in Georgia. © The American Society of Tropical Medicine and Hygiene.

[Right branch pulmonary artery stenosis with supravalvar aortic stenosis as a complication of Lecompte maneuver for tetralogy of Fallot associated with absent pulmonary valve].

PubMed

Honda, Yoshihiro; Suzuki, Shoji; Kaga, Shigeaki; Yoshida, Yukiyo; Kimura, Mitsuhiro; Kamiya, Kentaro; Sakakibara, Kenji; Katsu, Masatake

2015-05-01

The patient was diagnosed with tetralogy of Fallot associated with absent pulmonary valve syndrome and a low birth weight of 1,912 g. He suffered from respiratory distress on day 14 and received non-invasive positive pressure ventilation. At 5 months of age and 4.1 kg, he underwent intracardiac repair including right ventricular outflow repair with a monocusp patch, patch closure of the ventricular septum defect and right pulmonary transposition to the anterior of the ascending aorta following the Lecompte maneuver for airway decompression. He was subsequently discharged to home and exhibited an uneventful clinical course with non-invasive positive pressure ventilation for 5 months postoperatively. However, right pulmonary artery and supra-aortic stenosis was noted 2 years after the operation. Computed tomography (CT) and angiography showed ascending aorta strangulation by the right pulmonary artery with right ventricular outflow regurgitation. Right pulmonary artery reconstruction using polytetrafluoroethylene graft interposition and repeat right ventricular outflow repair with bicuspid hand-sewn valves was therefore performed;the postoperative course was uneventful. Pre- and post-operative management using non-invasive positive pressure ventilation and airway decompression with pulmonary artery translocation is a useful strategy in patients exhibiting symptomatic tetralogy of Fallot associated with absent pulmonary valve syndrome in the neonatal period.

Anomalous pulmonary venous connection: An underestimated entity.

PubMed

Magalhães, Sara P; Moreno, Nuno; Loureiro, Marília; França, Manuela; Reis, Fernanda; Alvares, Sílvia; Ribeiro, Manuel

2016-12-01

Anomalous pulmonary venous connection is an uncommon congenital anomaly in which all (total form) or some (partial form) pulmonary veins drain into a systemic vein or into the right atrium rather than into the left atrium. The authors present one case of total anomalous pulmonary venous connection and two cases of partial anomalous pulmonary venous connection, one of supracardiac drainage into the brachiocephalic vein, and the other of infracardiac anomalous venous drainage (scimitar syndrome). Through the presentation of these cases, this article aims to review the main pulmonary venous developmental defects, highlighting the role of imaging techniques in the assessment of these anomalies. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Comparison of metabolic syndrome with growing epidemic syndrome Z in terms of risk factors and gender differences.

PubMed

Uyar, Meral; Davutoğlu, Vedat; Aydın, Neriman; Filiz, Ayten

2013-05-01

The aim of this study is to compare metabolic syndrome with syndrome Z growing epidemic in terms of risk factors, demographic variables, and gender differences in our large cohort at southeastern area in Turkey. Data of patients admitted to sleep clinic in University of Gaziantep from January 2006 to January 2011 were retrospectively evaluated. ATP III and JNC 7 were used for defining metabolic syndrome and hypertension. Data of 761 patients were evaluated. Hypertension, diabetes mellitus, coronary artery disease, pulmonary hypertension, and left ventricular hypertrophy were more common in patients with syndrome Z than in patients without metabolic syndrome. Age, waist/neck circumferences, BMI, triglyceride, glucose, and Epworth sleepiness scale score were detected higher, whereas the minimum oxygen saturation during sleep was lower in patients with syndrome Z. Metabolic syndrome was more common in sleep apneic subjects than in controls (58 versus 30 %). Female sleep apneics showed higher rate of metabolic syndrome than those of males (74 versus 52 %). Hypertension, diabetes mellitus, coronary artery disease, and left ventricular hypertrophy were detected higher in males with syndrome Z than in males without metabolic syndrome. Snoring and excessive daytime sleepiness were detected higher in females with syndrome Z than in females without metabolic syndrome. Systemic/pulmonary hypertension, diabetes mellitus, and left ventricular hypertrophy were more common in females with syndrome Z than in females without metabolic syndrome. Complaints of headache and systemic/pulmonary hypertension were more common among females than males with syndrome Z. Female syndrome Z patients had lower minimum oxygen saturation than male patients with syndrome Z. Metabolic syndrome in sleep apneic patients is more prevalent than in controls. All metabolic syndrome parameters were significantly different among obstructive sleep apneic patients with respect to gender with more severe

Diseases of Pulmonary Surfactant Homeostasis

PubMed Central

Whitsett, Jeffrey A.; Wert, Susan E.; Weaver, Timothy E.

2015-01-01

Advances in physiology and biochemistry have provided fundamental insights into the role of pulmonary surfactant in the pathogenesis and treatment of preterm infants with respiratory distress syndrome. Identification of the surfactant proteins, lipid transporters, and transcriptional networks regulating their expression has provided the tools and insights needed to discern the molecular and cellular processes regulating the production and function of pulmonary surfactant prior to and after birth. Mutations in genes regulating surfactant homeostasis have been associated with severe lung disease in neonates and older infants. Biophysical and transgenic mouse models have provided insight into the mechanisms underlying surfactant protein and alveolar homeostasis. These studies have provided the framework for understanding the structure and function of pulmonary surfactant, which has informed understanding of the pathogenesis of diverse pulmonary disorders previously considered idiopathic. This review considers the pulmonary surfactant system and the genetic causes of acute and chronic lung disease caused by disruption of alveolar homeostasis. PMID:25621661

Parasitic pulmonary eosinophilia.

PubMed

Chitkara, Rajinder K; Krishna, Ganesh

2006-04-01

Parasitic infections, although common in tropical and subtropical regions, are prevalent worldwide because of changing immigration patterns and in international travel. The burden of worm infection is enormous and the intensity of infection is usually high among the poor and in immunocompromised individuals. Pulmonary eosinophilia occurs in almost all metazoan infections. In the Western world, the most common infections are caused by Strongyloides, Ascaris, Toxocara, and Ancylostoma species. Most of the nematodes multiply within the human host and cause pulmonary eosinophilia during larval migration through the lungs. Despite larval migration through the lungs, there is usually no permanent lung damage. The result is an increased number of eosinophils in the airways or lung parenchyma with or without peripheral eosinophilia. Löffler's syndrome, visceral larva migrans, and tropical pulmonary eosinophilia are the most common infections that cause pulmonary eosinophilia. The most serious parasitic eosinophilic lung disease is tropical pulmonary eosinophilia, a disorder caused by the filarial worms Wuchereria bancrofti and Brugia malayi, in which cases have typically been reported to masquerade acute or refractory bronchial asthma. Increasing awareness, newer diagnostic techniques, preventative measures, and antiparasitic drugs are important in reducing the worldwide morbidity and mortality from parasitic helminths and protozoa. This review focuses on common and some uncommon causes of pulmonary parasitic eosinophilia and their manifestations, diagnosis, and management.

Creation of aorto-pulmonary window with pulmonary artery band is not good palliation for hypoplastic left heart syndrome.

PubMed

Hosein, Riad B M; Mehta, Chetan; Stickley, John; Mcguirk, Simon P; Jones, Timothy J; Brawn, William J; Barron, David J

2007-11-01

A small sub-group of patients with hypoplastic left heart syndrome (HLHS) have normal-sized ascending aorta and arch. An alternative to the Norwood I procedure in these patients is the creation of an aorto-pulmonary (AP) window with a distal pulmonary artery band (PAB). We reviewed our experience with this technique and compared outcomes to the Norwood procedure for HLHS. All patients treated for HLHS in a single institution between 1992 and 2005 were analysed. This identified 13 patients treated with AP window and PAB compared to 333 patients undergoing stage I Norwood procedure. An unrestrictive AP window was created and the main PA was banded. Patient records and echocardiograms were analysed. Median follow-up was 10 (IQR 0-655) days and 100% complete. There were seven early deaths (54%) in the AP window group and two conversions to Norwood circulation. This was a significantly worse outcome than for the Norwood procedure over the same period, which had an early mortality of 29% (p=0.03). Kaplan-Meier actuarial analysis demonstrated a continued survival benefit of the Norwood group at 6 months (p=0.0005). Deaths were due to either low cardiac output syndrome (n=4) or sudden unheralded arrest (n=3). This occurred despite aortic cross-clamp and circulatory arrest times being significantly lower in the AP window group compared to the Norwood group (35+/-27 vs 55+/-16 min, p<0.01 and 16+/-29 vs 55+/-20 min, p<0.01, respectively). No differences in arterial saturations or systolic blood pressure existed between the groups, but diastolic blood pressure was significantly lower in the AP window group at 27+/-10 mmHg compared to 42+/-8 mmHg in the Norwood group (p=0.01) with evidence of flow reversal in the descending aorta. Differences in diastolic blood pressure between groups were abolished after conversion to stage II. Despite favourable anatomy and shorter ischaemic times, the AP window/PAB technique has a poor outcome compared to the Norwood procedure for HLHS. Low

Effort Thrombosis Presenting as Pulmonary Embolism in a Professional Baseball Pitcher

PubMed Central

Bushnell, Brandon D.; Anz, Adam W.; Dugger, Keith; Sakryd, Gary A.; Noonan, Thomas J.

2009-01-01

Context: Effort thrombosis, or Paget-Schroetter’s syndrome, is a rare subset of thoracic outlet syndrome in which deep venous thrombosis of the upper extremity occurs as the result of repetitive overhead motion. It is occasionally associated with pulmonary embolism. This case of effort thrombosis and pulmonary embolus was in a 25-year-old major league professional baseball pitcher, in which the only presenting complaints involved dizziness and shortness of breath without complaints involving the upper extremity—usually, a hallmark of most cases of this condition. The patient successfully returned to play for 5 subsequent seasons at the major league level after multimodal treatment that included surgery for thoracic outlet syndrome. Objective: Though rare, effort thrombosis should be included in the differential diagnosis of throwing athletes with traditional extremity-focused symptoms and in cases involving pulmonary or thoracic complaints. Rapid diagnosis is a critical component of successful treatment. PMID:23015912

Pulmonary hypoplasia-diaphragmatic hernia-anophthalmia-cardiac defect (PDAC) syndrome due to STRA6 mutations--what are the minimal criteria?

PubMed

Segel, Reeval; Levy-Lahad, Ephrat; Pasutto, Francesca; Picard, Elie; Rauch, Anita; Alterescu, Gheona; Schimmel, Michael S

2009-11-01

Microphthalmic syndrome 9 (OMIM601186) is a genetically and phenotypically variable condition, comprising anophthalmia, pulmonary hypoplasia, diaphragmatic hernia, and cardiac malformations (PDAC syndrome). Reported cases have all been associated with fetal/neonatal death or developmental delay. Recessive stimulated by retinoic acid gene 6 homolog (STRA6) mutations have recently been identified as the cause of cases of PDAC in which distinct, "bushy" eyebrows have been observed. We describe a patient with clinical anophthalmia, bushy eyebrows, patent ductus arteriosus, and normal development at age 30 months, who is a compound heterozygote for two novel STRA6 missense mutations. This patient's phenotype is consistent with the multisystemic malformations of PDAC syndrome, but is somewhat milder. This is the first living patient with compound heterozygous STRA6 mutations, which may explain her milder phenotype. We conclude that STRA6 analysis should be considered in all patients with clinical anophthalmia. Genetic counseling should be cautious with respect to long-term developmental outcomes. Copyright 2009 Wiley-Liss, Inc.

Pulmonary hypertension and vasculopathy in incontinentia pigmenti: a case report

PubMed Central

Alshenqiti, Abduljabbar; Nashabat, Marwan; AlGhoraibi, Hissah; Tamimi, Omar; Alfadhel, Majid

2017-01-01

Incontinentia pigmenti (IP; Bloch–Sulzberger syndrome) is a rare, genetic syndrome inherited as an X-linked dominant trait. It primarily affects female infants and is lethal in the majority of males during fetal life. The clinical findings include skin lesions, developmental defects, and defects of the eyes, teeth, skeletal system, and central nervous system. Cardiovascular complications of this disease in general, and pulmonary hypertension in particular, are extremely rare. This report describes the case of a 3-year-old girl with IP complicated by pulmonary arterial hypertension. Extensive cardiology workup done to the patient indicates underlying vasculopathy. This report sheds light on the relationship between IP and pulmonary hypertension, reviews the previously reported cases, and compares them with the reported case. PMID:28533687

Pulmonary hypertension and vasculopathy in incontinentia pigmenti: a case report.

PubMed

Alshenqiti, Abduljabbar; Nashabat, Marwan; AlGhoraibi, Hissah; Tamimi, Omar; Alfadhel, Majid

2017-01-01

Incontinentia pigmenti (IP; Bloch-Sulzberger syndrome) is a rare, genetic syndrome inherited as an X-linked dominant trait. It primarily affects female infants and is lethal in the majority of males during fetal life. The clinical findings include skin lesions, developmental defects, and defects of the eyes, teeth, skeletal system, and central nervous system. Cardiovascular complications of this disease in general, and pulmonary hypertension in particular, are extremely rare. This report describes the case of a 3-year-old girl with IP complicated by pulmonary arterial hypertension. Extensive cardiology workup done to the patient indicates underlying vasculopathy. This report sheds light on the relationship between IP and pulmonary hypertension, reviews the previously reported cases, and compares them with the reported case.

Use of Aminocaproic Acid in Combination With Extracorporeal Membrane Oxygenation in a Case of Leptospirosis Pulmonary Hemorrhage Syndrome.

PubMed

Pardinas, Miguel; Mendirichaga, Rodrigo; Budhrani, Gaurav; Garg, Rajan; Rosario, Luis; Rico, Rene; Panos, Anthony; Baier, Horst; Krick, Stefanie

2017-01-01

A 32-year-old man presented with a 10-day history of fever, chills, nausea, vomiting, myalgia, nonproductive cough, and worsening dyspnea after freshwater swimming in the Caribbean 1 week prior to presentation. Shortly after arrival at the hospital, the patient developed severe respiratory distress with massive hemoptysis. Based on serologic workup, he was diagnosed with leptospirosis pulmonary hemorrhage syndrome leading to diffuse alveolar hemorrhage, severe hypoxemic respiratory failure, and multiorgan failure. He received appropriate antibiotic coverage along with hemodynamic support with norepinephrine and vasopressin, mechanical ventilation, and renal replacement therapy in an intensive care unit. Introduction of extracorporeal membrane oxygenation was initiated to provide lung-protective ventilation supporting the recovery of his pulmonary function. Aminocaproic acid was used to stop and prevent further alveolar hemorrhage. He fully recovered thereafter; however, it is uncertain whether it was the use of aminocaproic acid that led to the resolution of his disease.

[Horseshoe lung with normal pulmonary venous return].

PubMed

Gondra Sangroniz, A; Elorz Lambarri, J; Villar Alvarez, M A; Lecumberri Cortes, I; Ayala Curiel, J

2010-09-01

Horseshoe lung is a rare congenital anomaly characterised by a midline isthmus of pulmonary parenchyma connecting the posterior basal segments of the lungs behind the heart in conjunction with unilateral pulmonary hypoplasia. Of all cases, 80% are associated with scimitar syndrome, consisting of right anomalous pulmonary venous drainage, pulmonary hypoplasia of the right lung and systemic arterial perfusion to some lung areas. A six year old girl who had recurrent lower respiratory infections since birth. Chest Rx, angioCT and MR showed: hypoplasia of the right lung, dextrocardia and pulmonary isthmus bridging both lungs behind the pericardium. The right hypoplastic lung had little systemic supply coming from the abdominal aorta. The right pulmonary artery was hypoplastic. The right pulmonary venous drainage was normal. We present a case of horseshoe lung without abnormal venous drainage. 2010 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Respiratory symptoms are poor predictors of concomitant chronic obstructive pulmonary disease in patients with primary Sjögren's syndrome.

PubMed

Strevens Bolmgren, Victor; Olsson, Peter; Wollmer, Per; Hesselstrand, Roger; Mandl, Thomas

2017-05-01

Involvement of the respiratory system, in particular dry airways and chronic obstructive pulmonary disease (COPD), is common in patients with primary Sjögren's syndrome (pSS). As respiratory symptoms are also common in pSS patients and may have different etiologies, we wanted to evaluate the amount and impact of respiratory symptoms in out-patients with pSS and to assess if such symptoms are related to concomitant COPD. The St George's Respiratory Questionnaire (SGRQ) was used to assess respiratory symptoms. SGRQ scores were compared between 51 consecutive pSS patients, in an out-patient setting, and 80 population-based controls. The patients were also studied by pulmonary function tests and CT scans of the lungs to assess signs of obstructive airway disease, including COPD, as well as to assess signs of interstitial lung disease (ILD). 41 and 18% of pSS patients were found to have COPD and radiographic signs of ILD, respectively. pSS patients had significantly higher SGRQ scores compared to controls, but no significant differences in SGRQ scores were found between patients with and without COPD. Neither did the small group of pSS patients with ILD significantly differ in SGRQ scores in comparison to patients without ILD. Respiratory symptoms were common in pSS, but were not more common in patients with concomitant COPD. Since pulmonary involvement in pSS is associated with an increased mortality and respiratory symptoms is a poor marker for pulmonary involvement, we suggest that pulmonary function tests should be performed liberally in all pSS patients regardless of symptoms.

Anomalous Origin of Coronary Artery From Main Pulmonary Artery in Hypoplastic Left Heart Syndrome.

PubMed

Turiy, Yuliya; Douglas, William; Balaguru, Duraisamy

2015-12-01

We report a case of anomalous origin of the left anterior descending coronary artery (LAD) from the main pulmonary artery in a child with hypoplastic left heart syndrome (mitral atresia/aortic atresia). Mechanical circulatory support was necessary because of the inability to wean from cardiopulmonary bypass after the Norwood procedure. The patient died at 4 months of age having continued depressed right ventricular function. The diagnosis was made during a catheterization performed 6 weeks after surgery because of concern for stenosis of Blalock-Taussig shunt. We believe his prolonged postoperative recovery and eventual demise can partially be attributed to lack of cardioplegia to the anomalous LAD territory during surgery. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Management of pulmonary arterial hypertension associated with congenital heart disease.

PubMed

Togănel, Rodica; Benedek, I; Suteu, Carmen; Blesneac, Cristina

2007-01-01

Congenital heart diseases are the most common congenital malformations and account for about eight cases per 1000 births and are often associated with pulmonary arterial hypertension. Increased shear stress and the excess flow through the pulmonary vascular bed due to a systemic-to-pulmonary shunt lead to the development of pulmonary vascular disease and an increase in pulmonary vascular resistance. Without surgical repair approximately 30% of patients develop pulmonary vascular disease. Eisenmenger syndrome represents the extreme end of pulmonary arterial hypertension with congenital heart disease. We summarized the current therapeutic options for pulmonary arterial hypertension; conventional treatments including calcium channel blockers, anticoagulation, digitalis, diuretics, and new treatment: prostacyclin, bosentan, sildenafil, ambrisentan. Preliminary data of new therapies are encouraging with disease significantly improved natural history, but there is need for more evidence-based data.

Use of Aminocaproic Acid in Combination With Extracorporeal Membrane Oxygenation in a Case of Leptospirosis Pulmonary Hemorrhage Syndrome

PubMed Central

Pardinas, Miguel; Mendirichaga, Rodrigo; Budhrani, Gaurav; Garg, Rajan; Rosario, Luis; Rico, Rene; Panos, Anthony; Baier, Horst; Krick, Stefanie

2017-01-01

A 32-year-old man presented with a 10-day history of fever, chills, nausea, vomiting, myalgia, nonproductive cough, and worsening dyspnea after freshwater swimming in the Caribbean 1 week prior to presentation. Shortly after arrival at the hospital, the patient developed severe respiratory distress with massive hemoptysis. Based on serologic workup, he was diagnosed with leptospirosis pulmonary hemorrhage syndrome leading to diffuse alveolar hemorrhage, severe hypoxemic respiratory failure, and multiorgan failure. He received appropriate antibiotic coverage along with hemodynamic support with norepinephrine and vasopressin, mechanical ventilation, and renal replacement therapy in an intensive care unit. Introduction of extracorporeal membrane oxygenation was initiated to provide lung-protective ventilation supporting the recovery of his pulmonary function. Aminocaproic acid was used to stop and prevent further alveolar hemorrhage. He fully recovered thereafter; however, it is uncertain whether it was the use of aminocaproic acid that led to the resolution of his disease. PMID:28469503

Takotsubo cardiomyopathy after treatment of pulmonary arterial hypertension

PubMed Central

Cork, David P.; Mehrotra, Amit K.; Gomberg-Maitland, Mardi

2012-01-01

Pulmonary arterial hypertension is a fatal disease. Intravenous prostanoids are often utilized for long-term management of patients. The therapy requires a significant commitment and change in lifestyle for both the patient and family. Takotsubo cardiomyopathy, transient apical ballooning syndrome, has been reported in association with emotional and physical stress. This case report describes a patient with pulmonary arterial hypertension who developed Takotsubo cardiomyopathy after treatment initiation with intravenous treprostinil. Over time, the syndrome resolved and the patient had return of normal left ventricular function. Takotsubo cardiomyopathy should be recognized as a potential, rare complication of therapy initiation due to the severity of the illness and the emotional stress of the disease. PMID:23130109

Clinical Characteristics and Prognosis of Pulmonary Embolism Caused by Economy Class Syndrome.

PubMed

Abellás, María; Menéndez, Ana; Morillo, Raquel; Jara-Palomares, Luis; Barrios, Deisy; Nieto, Rosa; Barbero, Esther; Corres, Jesús; Ruiz-Artacho, Pedro; Jiménez, David

2017-09-01

Clinical presentation and short-term prognosis of patients with travel-associated acute pulmonary embolism (PE) (i.e., economy class syndrome [ECS]) is not well understood. In this retrospective cohort study of patients with acute PE identified from a single center registry, we assessed the clinical presentation and the association between ECS and the outcomes of all-cause mortality, PE-related mortality, nonfatal venous thromboembolism and nonfatal major bleeding rates through 30days after initiation of PE treatment. Of the 2,333 patients with acute symptomatic PE, 124 (5.3%; 95% confidence interval, 4.4-6.3%) had ECS. Patients with ECS were younger and had fewer comorbid diseases (recent bleeding, chronic obstructive pulmonary disease, congestive heart failure), but they presented with more signs of clinical severity (syncope [48% vs. 14%; P<.001], tachycardia [37% vs. 21%; P<.001], right ventricular dysfunction [31% vs. 19%; P<.01] and myocardial injury [57% vs. 28%; P<.001]) compared to those without ECS. Regression analyses showed a significantly lower risk of all-cause mortality for patients with ECS compared to patients without ECS (1.6% vs. 9.6%; P<.01). We did not detect a difference in PE-related mortality at 30days between those with and those without ECS (0.8% vs. 3.1%; P=.18). PE patients with ECS are younger and have fewer comorbid diseases compared to those without ECS. Though they present with more signs of clinical severity, their short-term prognosis is excellent. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Swyer-James syndrome associated with Noonan syndrome: report of a case.

PubMed

Lin, Y M; Huang, W L; Hwang, J J; Ko, Y L; Lien, W P

1995-12-01

A 28-year-old man with Noonan syndrome associated with unilateral hyperlucent lung is reported. He had the typical craniofacial appearance and short stature of Noonan syndrome; he had mild mental retardation, atrophic testis, mild funnel chest and kyphosis. cardiovascular abnormalities included asymmetric hypertrophic cardiomyopathy and a significantly different caliber of the left and right pulmonary arteries. The unilateral hyperlucent lung was shown to result from acquired nondestructive emphysema caused by nonvalvular obstruction of the bronchi (Swyer-James syndrome or Macleod's syndrome). To the authors' knowledge, this is the first reported case of Noonan syndrome associated with Swyer-James syndrome.

Immune reconstitution inflammatory syndrome in acquired immunodeficiency syndrome.

PubMed

Jindal, A; Duggal, L; Jain, N; Malhotra, S

2008-01-01

A 33-year-old male presented with a history of fever and cough and was diagnosed to have pulmonary tuberculosis and acquired immunodeficiency syndrome (AIDS). He was started on antituberculosis therapy (ATT) followed by highly active anti-retroviral treatment (HAART) after one week. He developed an immune reconstitution inflammatory syndrome (IRIS) leading to an exacerbation of the tuberculosis disease. After HAART was stopped his condition improved dramatically.

Refeeding syndrome.

PubMed

Fernández López, M T; López Otero, M J; Alvarez Vázquez, P; Arias Delgado, J; Varela Correa, J J

2009-01-01

Refeeding syndrome is a complex syndrome that occurs as a result of reintroducing nutrition (oral, enteral or parenteral) to patients who are starved or malnourished. Patients can develop fluid-balance abnormalities, electrolyte disorders (hypophosphataemia, hypokalaemia and hypomagnesaemia), abnormal glucose metabolism and certain vitamin deficiencies. Refeeding syndrome encompasses abnormalities affecting multiple organ systems, including neurological, pulmonary, cardiac, neuromuscular and haematological functions. Pathogenic mechanisms involved in the refeeding syndrome and clinical manifestations have been reviewed. We provide suggestions for the prevention and treatment of refeeding syndrome. The most important steps are to identify patients at risk, reintroduce nutrition cautiously and correct electrolyte and vitamin deficiencies properly.

The myth of the Bernheim syndrome.

PubMed

Chung, Monica S; Ko, Jo Mi; Chamogeorgakis, Themistokles; Hall, Shelley A; Roberts, William C

2013-10-01

The Bernheim syndrome has been a topic of discussion for over a century. It has been reported to be caused by severe rightward movement of the ventricular septum resulting in compression of the right ventricular cavity leading to right-sided heart failure without pulmonary congestion. Hemodynamic findings have been described in a few patients with the so-called Bernheim syndrome. We describe a patient in whom the ventricular septum dramatically decreased the size of the right ventricular cavity and yet peak systolic pressures in both the right ventricle and pulmonary trunk were identical. Thus, it is difficult to view the Bernheim syndrome as a real entity.

LEOPARD syndrome: what are café noir spots?

PubMed

Rodríguez-Bujaldón, Alfonso; Vazquez-Bayo, Carmen; Jimenez-Puya, Rafael; Galan-Gutierrez, Manuel; Moreno-Gimenez, José; Rodriguez-Garcia, Alfonso; Tercedor, Jesus; Velez-Garcia, Antonio

2008-01-01

Lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retarded growth, and deafness syndrome (multiple lentigines syndrome) is most often characterized by multiple lentigines and cardiac conduction defects. Café noir spot is a term proposed, by analogy to café au lait spots, for the larger and darkly pigmented patches that are frequently observed in patients with this syndrome. Although presumed by some authors to represent lentigines, the histologic features of café noir spots have not been well documented in the literature. Only two previous cases have been reported in which a biopsy of the café noir spots than melanocytic nevi. We describe the histologic characteristics of seven café noir spots in six patients with lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retarded growth, and deafness syndrome. Three lesions represented melanocytic nevi (one with dysplastic features), and four were compatible with lentigo simplex. These findings help our understanding of the histologic spectrum of pigmented lesions in lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retarded growth, and deafness syndrome.

Mounier Kuhn syndrome presenting with recurrent atelectasis.

PubMed

Quentin, Christine; Lefevre, Nicolas; Bodart, Eddy; Hanssens, Laurence

2017-09-11

Objective and importance Mounier Kuhn syndrome is usually diagnosed in adulthood, and only a few cases have been described in childhood. Clinical presentation We present the case of a seven-year-old boy suffering from recurrent pneumonia and atelectasis. Intervention Previously performed chest X-rays showed bilateral hyperinflation and tracheobronchomegaly. Chest computed tomography (CT) confirmed the presence of distal enlargement of trachea and bronchi. Tracheobronchomegaly associated with recurrent respiratory tract infections is consistent with Mounier Kuhn syndrome. Pseudomonas aeruginosa was isolated from the sputum of the patient. He was then treated according to the guidelines for P. aeruginosa management in cystic fibrosis patients considering the similarities in clinical presentations and pathophysiology of both diseases. Antibiotic treatment resulted in a remarkable reduction of events of pulmonary exacerbation and hospitalizations. There are no specific guidelines for treatment options in case of pulmonary exacerbation of Mounier Kuhn syndrome. Case reports discussing the choice and efficiency of antibiotic treatment are random. Conclusion headings We share our experience of treating pulmonary exacerbation caused by P. aeruginosa in a patient with Mounier Kuhn syndrome suggesting a possible treatment option of pseudomonas infections in this syndrome.

Vascular Ehlers-Danlos syndrome with cryptorchidism, recurrent pneumothorax, and pulmonary capillary hemangiomatosis-like foci: A case report.

PubMed

Park, Min A; Shin, So Youn; Kim, Young Jin; Park, Myung Jae; Lee, Seung Hyeun

2017-11-01

Vascular Ehlers-Danlos syndrome (vEDS) is a rare autosomal dominant inherited collagen disorder caused by defects or deficiency of pro-alpha 1 chain of type III procollagen encoded by COL3A1. vEDS is characterized not only by soft tissue manifestations including hyperextensibility of skin and joint hypermobility but also by early mortality due to rupture of arteries or vital organs. Although pulmonary complications are not common, vEDS cases complicated by pneumothorax, hemothorax, or intrapulmonary hematoma have been reported. When a patient initially presents only with pulmonary complications, it is not easy for clinicians to suspect vEDS. We report a case of an 18-year-old high school student, with a past history of cryptorchidism, presenting with recurrent pneumothorax. Routine laboratory findings were unremarkable. Chest high resolution computed tomographic scan showed age-unmatched hyperinflation of both lungs, atypical cystic changes and multifocal ground glass opacities scattered in both lower lobes. His slender body shape, hyperflexible joints, and hyperextensible skin provided clue to suspicion of a possible connective tissue disorder. The histological examination of the lung lesions showed excessive capillary proliferation in the pulmonary interstitium and pleura allowing the diagnosis of pulmonary capillary hemangiomatosis (PCH)-like foci. Genetic study revealed COL3A1 gene splicing site mutation confirming his diagnosis as vEDS. Although his diagnosis vEDS is notorious for fatal vascular complication, there was no evidence of such complication at presentation. Fortunately, he has been followed up for 10 months without pulmonary or vascular complications. To the best of our knowledge, both cryptorchidism and PCH-like foci have never been reported yet as complications of vEDS, suggesting our case might be a new variant of this condition. This case emphasizes the importance of comprehensive physical examination and history-taking, and the clinical

Hantavirus Pulmonary Syndrome in Santa Cruz, Bolivia: Outbreak Investigation and Antibody Prevalence Study

DTIC Science & Technology

2012-10-18

transmission, is vast, including the Amazon Basin of Brazil and contiguous lowlands of Peru , Bolivia, and Paraguay [13–17]. Assuming that the episode of...U.S. Naval Medical Research Unit 6, Lima, Peru , 3 Bolivian National Center for Tropical Diseases, Santa Cruz, Bolivia, 4 Argentine National Institute...preceding the outbreak was particularly heavy in comparison to other years, suggesting a possible climatic or ecological influence on rodent populations

Chest MR imaging in the follow-up of pulmonary alterations in paediatric patients with middle lobe syndrome: comparison with chest X-ray.

PubMed

Fraioli, F; Serra, G; Ciarlo, G; Massaccesi, V; Liberali, S; Fiorelli, A; Macrì, F; Catalano, C

2013-04-01

The authors evaluated the role of magnetic resonance (MR) imaging of the chest in comparison with chest X-ray in the follow-up of pulmonary abnormalities detected by computed tomography (CT) in paediatric patients with middle lobe syndrome. Seventeen patients with middle lobe syndrome (mean age 6.2 years) underwent chest CT at the time of diagnosis (100 kV, CARE dose with quality reference of 70 mAs; collimation 24×1.2 mm; rotation time 0.33 s; scan time 5 s); at follow-up after a mean of 15.3 months, all patients were evaluated with chest MR imaging with a respiratory-triggered T2-weighted BLADE sequence (TR 2,000; TE 27 ms; FOV 400 mm; flip angle 150°; slice thickness 5 mm) and chest X-ray. Images from each modality were assessed for the presence of pulmonary consolidations, bronchiectases, bronchial wall thickening and mucous plugging. Hilar and mediastinal lymphadenopathies were assessed on CT and MR images. Baseline CT detected consolidations in 100% of patients, bronchiectases in 35%, bronchial wall thickening in 53% and mucous plugging in 35%. MR imaging and chest X-ray identified consolidations in 65% and 35%, bronchiectases in 35% and 29%, bronchial wall thickening in 59% and 6% and mucous plugging in 25% and 0%, respectively. Lymphadenopathy was seen in 64% of patients at CT and in 47% at MR imaging. Patients with middle lobe syndrome show a wide range of parenchymal and bronchial abnormalities at diagnosis. Compared with MR imaging, chest X-ray seems to underestimate these changes. Chest MR imaging might represent a feasible and radiation-free option for an overall assessment of the lung in the follow-up of patients with middle lobe syndrome.

Mirror Syndrome assocciated with Patau Syndrome: A Case Report.

PubMed

Pais, Ana Sofia; Areia, Ana Luísa Fialho Amaral de; Franco, Sofia Margarida Perienes; Fonseca, Etelvina Morais Ferreira; Moura, José Paulo Achando Silva

2018-05-16

Mirror syndrome is an unusual pathological condition in which maternal edema in pregnancy is seen in association with severe fetal and/or placental hydrops. The disease can be life-threatening for both the mother and the fetus. The pathogenesis is poorly understood, and may be confused with preeclampsia, even though distinguishing features can be identified. We report a rare case of mirror syndrome with maternal pulmonary edema associated with fetal hydrops due to Patau syndrome. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

Pulmonary Mechanics and Mortality in Mechanically Ventilated Patients Without Acute Respiratory Distress Syndrome: A Cohort Study.

PubMed

Fuller, Brian M; Page, David; Stephens, Robert J; Roberts, Brian W; Drewry, Anne M; Ablordeppey, Enyo; Mohr, Nicholas M; Kollef, Marin H

2018-03-01

Driving pressure has been proposed as a major determinant of outcome in patients with acute respiratory distress syndrome (ARDS), but there is little data examining the association between pulmonary mechanics, including driving pressure, and outcomes in mechanically ventilated patients without ARDS. Secondary analysis from 1,705 mechanically ventilated patients enrolled in a clinical study that examined outcomes associated with the use of early lung-protective mechanical ventilation. The primary outcome was mortality and the secondary outcome was the incidence of ARDS. Multivariable models were constructed to: define the association between pulmonary mechanics (driving pressure, plateau pressure, and compliance) and mortality; and evaluate if driving pressure contributed information beyond that provided by other pulmonary mechanics. The mortality rate for the entire cohort was 26.0%. Compared with survivors, non-survivors had significantly higher driving pressure [15.9 (5.4) vs. 14.9 (4.4), P = 0.005] and plateau pressure [21.4 (5.7) vs. 20.4 (4.6), P = 0.001]. Driving pressure was independently associated with mortality [adjusted OR, 1.04 (1.01-1.07)]. Models related to plateau pressure also revealed an independent association with mortality, with similar effect size and interval estimates as driving pressure. There were 152 patients who progressed to ARDS (8.9%). Along with driving pressure and plateau pressure, mechanical power [adjusted OR, 1.03 (1.00-1.06)] was also independently associated with ARDS development. In mechanically ventilated patients, driving pressure and plateau pressure are risk factors for mortality and ARDS, and provide similar information. Mechanical power is also a risk factor for ARDS.

[Pulmonary manifestations in systemic lupus erythematosus].

PubMed

Vincze, Krisztina; Odler, Balázs; Müller, Veronika

2016-07-01

Systemic lupus erythematosus is the most common connective tissue disease that is associated with pulmonary manifestations. Although lupus has the potential to affect any organ, lung involvement is observed during the course of the disease in most cases and it is prognostic for outcome. Pulmonary manifestations in lupus can be classified into five groups based on the anatomical involvement: pleura, lung parenchyma, bronchi and bronchioli, lung vasculature and respiratory muscles can be involved. The most common respiratory manifestations attributable to lupus are pleuritis with or without pleural effusion, pulmonary vascular disease, upper and lower airway dysfunction, parenchymal disease, and diaphragmatic dysfunction (shrinking lung syndrome). In this article the authors summarize lung involvement of lupus, its diagnosis, therapy and prognosis. Orv. Hetil., 2016, 157(29), 1154-1160.

Role of nucleocapsid protein of hantaviruses in intracellular traffic of viral glycoproteins.

PubMed

Shimizu, Kenta; Yoshimatsu, Kumiko; Koma, Takaaki; Yasuda, Shumpei P; Arikawa, Jiro

2013-12-26

To understand the role of nucleocapsid protein (NP) of hantaviruses in viral assembly, the effect of NP on intracellular traffic of viral glycoproteins Gn and Gc was investigated. Double staining of viral and host proteins in Hantaan virus (HTNV)-infected Vero E6 cells showed that Gn and Gc were localized to cis-Golgi, in which virus particles are thought to be formed. When HTNV Gn and Gc were expressed by a plasmid encoding glycoprotein precursor (GPC), which is posttranslationally cleaved into Gn and Gc, Gn was localized to cis-Golgi, whereas Gc showed diffuse distribution in the cytoplasm in 32.9% of Gc-positive cells. The ratio of the diffused Gc-positive cells was significantly decreased to 15.0% by co-expression of HTNV NP. Co-expression of HTNV GPC with NPs of other hantaviruses, such as Seoul virus, Puumala virus and Sin Nombre virus, also reduced the ratios of diffused Gc-positive cells to 13.5%, 25.2%, and 11.6%, respectively. Among amino- and carboxyl-terminally truncated HTNV NPs, NP75-429, NP116-429, NP1-333, NP1-233, and NP1-155 possessed activity to reduce the ratio of diffused Gc-positive cells, while NP155-429 and NP1-116 did not. NP30-429 has partial activity. These results indicate that amino acid region 116-155 of NP is important for the activity, although amino acid region 1-30 is partially related. Truncation of the HTNV Gc cytoplasmic tail caused an increase in diffused Gc-positive cells. In addition, the effect of coexpression of HTNV NP was weakened. These results suggest that HTNV NP has a role to promote Golgi localization of Gc through a mechanism possibly mediated by the Gc cytoplasmic tail. Copyright © 2013 Elsevier B.V. All rights reserved.

Hemorrhagic Fever with Renal Syndrome (Korean Hemorrhagic Fever)

DTIC Science & Technology

1990-06-29

particles were used for a rapid serologic diagnostic test for HFRS. ’te-re were 430 cases of HFRS in Korea in 1989 and large outbreaks of scrub typhus...almost same as in 1988. A simple and rapid serologic diagnostic test for hantavirus infection was developed by high density particle agglutination...infection and HFRS b) serologic relation cif hantaviruses isolated from the different parts of the world c) development of a simple serologic diagnostic

Concurrent variant type 3 autoimmune polyglandular syndrome and pulmonary arterial hypertension in a Japanese woman.

PubMed

Iijima, Toshie; Niitani, Takafumi; Tanaka, Seiichi; Yanagi, Kazunori; Jojima, Teruo; Suzuki, Kunihiro; Usui, Isao; Aso, Yoshimasa

2018-04-26

We describe a very rare case of concurrent variant type 3 autoimmune polyglandular syndrome (APS) and pulmonary arterial hypertension (PAH). A previously healthy 65-year-old Japanese woman was referred to our university hospital with a 2-month history of general fatigue and hyperglycemia. Laboratory tests revealed severe hyperglycemia (plasma glucose 543 mg/dL and HbA1c 10.7%) with ketonuria (3+). Glutamic acid decarboxylase (GAD) and IA-2 antibodies were positive, and the serum C peptide level was markedly decreased to 0.2 ng/mL. Accordingly, type 1 diabetes was diagnosed. Hashimoto's thyroiditis was also diagnosed because she had a diffuse goiter and a mild hypothyroidism (TSH 8.20 μU/mL, and FT4 0.80 ng/mL) with positive autoantibodies for thyroid peroxidase and thyroglobulin. There was neither adrenal insufficiency nor hypocalcemia. In addition, chest X ray showed a suspicious PAH by a dilation of both pulmonary arteries, especially right descending artery, and right heart catheterization confirmed the presence of PAH. HLA Class II genotyping revealed DRB1-DQB1*0901-*0303, a common susceptibility haplotype in Japanese patients with type 3 APS or acute-onset type 1 diabetes. The combination of variant type 3 APS and PAH is extremely rare and to the best of knowledge, this is the first case reported in a Japanese patient.

Prenatal diagnosis of Berry syndrome by fetal echocardiography: a case report.

PubMed

Yang, Shui-Hua; Tian, Xiao-Xian; Li, Yuan-Yuan; Yang, Zuo-Jian

2016-10-01

We report a case in which Berry syndrome is diagnosed by fetal echocardiography. Fetal echocardiography showed that the ascending aorta, main pulmonary artery, left pulmonary artery, and right pulmonary artery were presented as a vascular complexity in the three vessels and pulmonary arterial branches view. © 2016, Wiley Periodicals, Inc.

Death-domain associated protein-6 (DAXX) mediated apoptosis in hantavirus infection is counter-balanced by activation of interferon-stimulated nuclear transcription factors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khaiboullina, Svetlana F., E-mail: sv.khaiboullina@gmail.com; Morzunov, Sergey P.; Boichuk, Sergei V.

2013-09-01

Hantaviruses are negative strand RNA species that replicate predominantly in the cytoplasm. They also activate numerous cellular responses, but their involvement in nuclear processes is yet to be established. Using human umbilical vein endothelial cells (HUVECs), this study investigates the molecular finger-print of nuclear transcription factors during hantavirus infection. The viral-replication-dependent activation of pro-myelocytic leukemia protein (PML) was followed by subsequent localization in nuclear bodies (NBs). PML was also found in close proximity to activated Sp100 nuclear antigen and interferon-stimulated gene 20 kDa protein (ISG-20), but co-localization with death-domain associated protein-6 (DAXX) was not observed. These data demonstrate that hantavirusmore » triggers PML activation and localization in NBs in the absence of DAXX-PLM-NB co-localization. The results suggest that viral infection interferes with DAXX-mediated apoptosis, and expression of interferon-activated Sp100 and ISG-20 proteins may indicate intracellular intrinsic antiviral attempts.« less

Recurrence of non-cardiogenic pulmonary edema and sustained hypotension shock in cystic pheochromocytoma.

PubMed

Dai, Jin; Chen, Shen-Jie; Yang, Bing-Sheng; Lü, Shu-Min; Zhu, Min; Xu, Yi-Fei; Chen, Jie; Cai, Hong-Wen; Mao, Wei

2017-05-01

Pheochromocytoma is a rare neuroendocrine tumor which derives from chromaffin cells of the adrenal gland or relevant to sympathetic nerves and ganglia. The clinical features of pheochromocytoma are various. Paroxysmal episodes of serious hypertension, headache, palpitation, and diaphoresis are the typical manifestations (Bravo, 2004). Hypotension shock, pulmonary edema, and acute coronary syndrome induced by pheochromocytoma are uncommon (Malindretos et al., 2008; Batisse-Lignier et al., 2015). In this study, we present a rare case of cystic pheochromocytoma causing recurrent hypotension shock, non-cardiogenic pulmonary edema, and acute coronary syndrome, and the possible mechanisms are discussed.

Mutations in the G6PC3 gene cause Dursun syndrome.

PubMed

Banka, Siddharth; Newman, William G; Ozgül, R Koksal; Dursun, Ali

2010-10-01

Dursun syndrome is a triad of familial primary pulmonary hypertension, leucopenia, and atrial septal defect. Here we demonstrate that mutations in G6PC3 cause Dursun syndrome. Mutations in G6PC3 are known to also cause severe congenital neutropenia type 4. Identification of the genetic basis of Dursun syndrome expands the pre-existing knowledge about the phenotypic effects of mutations in G6PC3. We propose that Dursun syndrome should now be considered as a subset of severe congenital neutropenia type 4 with pulmonary hypertension as an important clinical feature. Copyright © 2010 Wiley-Liss, Inc.