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Slobodan Paessler - One of the best experts on this subject based on the ideXlab platform.
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the glycoprotein of the live attenuated junin virus vaccine strain induces endoplasmic reticulum stress and forms aggregates prior to degradation in the lysosome
Journal of Virology, 2020Co-Authors: John T. Manning, Alexey Seregin, Cheng Huang, Juan Carlos De La Torre, Takaaki Koma, Nadya Yun, Rachel A Sattler, Chiomah Ezeomah, Slobodan PaesslerAbstract:Argentine Hemorrhagic Fever is a potentially lethal disease that is caused by Junin virus (JUNV). There are currently around 5 million individuals at risk of infection within regions of endemicity in Argentina. The live attenuated vaccine strain Candid #1 (Can) is approved for use in regions of endemicity and has substantially decreased the number of annual Argentine Hemorrhagic Fever (AHF) cases. The glycoprotein (GPC) gene is primarily responsible for attenuation of the Can strain, and we have shown that the absence of an N-linked glycosylation motif in the subunit G1 of the glycoprotein complex of Can, which is otherwise present in the wild-type pathogenic JUNV, causes GPC retention in the endoplasmic reticulum (ER). Here, we show that Can GPC aggregates in the ER of infected cells, forming incorrect cross-chain disulfide bonds, which results in impaired GPC processing into G1 and G2. The GPC fails to cleave into its G1 and G2 subunits and is targeted for degradation within lysosomes. Cells infected with the wild-type Romero (Rom) strain do not produce aggregates that are observed in Can infection, and the stress on the ER remains minimal. While the mutation of the N-linked glycosylation motif (T168A) is primarily responsible for the formation of aggregates, other mutations within G1 that occurred earlier in the passage history of the Can strain also contribute to aggregation of the GPC within the ER.IMPORTANCE The development of vaccines and therapeutics to combat viral Hemorrhagic Fevers remains a top priority within the Implementation Plan of the U.S. Department of Health and Human Services Public Health Emergency Medical Countermeasures Enterprise. The Can strain, derived from the pathogenic XJ strain of JUNV, has been demonstrated to be both safe and protective against AHF. While the vaccine strain is approved for use in regions of endemicity within Argentina, the mechanisms of Can attenuation have not been elucidated. A better understanding of the viral genetic determinants of attenuation will improve our understanding of the mechanisms contributing to disease pathogenesis and provide critical information for the rational design of live attenuated vaccine candidates for other viral Hemorrhagic Fevers.
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Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine, Candid #1, Results in Its Improper Processing, and Reduced Surface Expression.
Frontiers in cellular and infection microbiology, 2017Co-Authors: John T. Manning, Alexey Seregin, Cheng Huang, Juan Carlos De La Torre, Takaaki Koma, Nadezhda E. Yun, José M. Barral, Slobodan PaesslerAbstract:Junin virus (JUNV), a highly pathogenic New World arenavirus, is the causative agent of Argentine Hemorrhagic Fever (AHF). The live-attenuated Candid #1 (Can) strain currently serves as a vaccine for at-risk populations. We have previously shown that the Can glycoprotein (GPC) gene is the primary gene responsible for attenuation in a guinea pig model of AHF. However, the mechanisms through which the GPC contributes to the attenuation of the Can strain remain unknown. A more complete understanding of the mechanisms underlying the attenuation and immunogenicity of the Can strain will potentially allow for the rational design of additional safe and novel vaccines. Here, we provide a detailed comparison of both RNA and protein expression profiles between both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain. The recombinant viruses that express Can GPC, which were shown to be attenuated in guinea pigs, displayed different RNA levels and GPC processing patterns as determined by Northern and Western blot analyses, respectively. Analysis of recombinant viruses containing amino acid substitutions selected at different mouse brain passages during the generation of Can revealed that altered Can GPC processing was primarily due to the T168A substitution within G1, which eliminates an N-linked glycosylation motif. Incorporation of the T168A substitution in the Rom GPC resulted in a Can-like processing pattern of Rom GPC. In addition, JUNV GPCs containing T168A substitution were retained within the endoplasmic reticulum (ER) and displayed significantly lower cell surface expression than wild-type Rom GPC. Interestingly, the reversion A168T in Can GPC significantly increased GPC expression at the cell surface. Our results demonstrate that recombinant JUNV expressing Can GPC display markedly different protein expression and elevated genomic RNA expression when compared to viruses expressing Rom GPC. Additionally, our findings indicate that the N-linked glycosylation motif at amino acid positions 166 to 168 is important for trafficking of JUNV GPC to the cell surface, and the elimination of this motif interferes with the GPC release from the ER.
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reactive astrogliosis in response to Hemorrhagic Fever virus microarray profile of junin virus infected human astrocytes
Virology Journal, 2014Co-Authors: Olga A Kolokoltsova, Nadezhda E. Yun, Slobodan PaesslerAbstract:Background Arenavirus Junin is the causative agent of Argentine Hemorrhagic Fever. Limited information is available concerning the pathogenesis of this human disease, especially the pathogenesis of acute and late neurological symptoms.
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potent inhibition of junin virus infection by interferon in murine cells
PLOS Neglected Tropical Diseases, 2014Co-Authors: Chengcheng Huang, Alexey Seregin, Ashley M. Grant, Nadezhda E. Yun, Olga A Kolokoltsova, Aida G Walker, Slobodan PaesslerAbstract:The new world arenavirus Junin virus (JUNV) is the causative agent of Argentine Hemorrhagic Fever, a lethal human infectious disease. Adult laboratory mice are generally resistant to peripheral infection by JUNV. The mechanism underlying the mouse resistance to JUNV infection is largely unknown. We have reported that interferon receptor knockout mice succumb to JUNV infection, indicating the critical role of interferon in restricting JUNV infection in mice. Here we report that the pathogenic and vaccine strains of JUNV were highly sensitive to interferon in murine primary cells. Treatment with low concentrations of interferon abrogated viral NP protein expression in murine cells. The replication of both JUNVs was enhanced in IRF3/IRF7 deficient cells. In addition, the vaccine strain of JUNV displayed impaired growth in primary murine cells. Our data suggested a direct and potent role of host interferon response in restricting JUNV replication in mice. The defect in viral growth for vaccine JUNV might also partially explain its attenuation in mice.
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Potent Inhibition of Junı́n Virus Infection by Interferon in
2013Co-Authors: Murine Cells, Cheng Huang, Ashley M. Grant, Nadezhda E. Yun, Olga A Kolokoltsova, Aida G Walker, Alexey V. Seregin, Slobodan PaesslerAbstract:The new world arenavirus Junı́n virus (JUNV) is the causative agent of Argentine Hemorrhagic Fever, a lethal human infectious disease. Adult laboratory mice are generally resistant to peripheral infection by JUNV. The mechanism underlying the mouse resistance to JUNV infection is largely unknown. We have reported that interferon receptor knockout mice succumb to JUNV infection, indicating the critical role of interferon in restricting JUNV infection in mice. Here we report that the pathogenic and vaccine strains of JUNV were highly sensitive to interferon in murine primary cells. Treatment with low concentrations of interferon abrogated viral NP protein expression in murine cells. The replication of both JUNVs was enhanced in IRF3/IRF7 deficient cells. In addition, the vaccine strain of JUNV displayed impaired growth in primary murine cells. Our data suggested a direct and potent role of host interferon response in restricting JUNV replication in mice. The defect in viral growth for vaccine JUNV might also partially explain its attenuation in mice
Marina B. Chiappero - One of the best experts on this subject based on the ideXlab platform.
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Effective Population Size Differences in Calomys musculinus, the Host of Junín Virus: Their Relationship with the Epidemiological History of Argentine Hemorrhagic Fever.
The American journal of tropical medicine and hygiene, 2018Co-Authors: Marina B. Chiappero, Cristina N. Gardenal, Gladys E. Calderón, M. F. Piacenza, María C. Provensal, Jaime PolopAbstract:Argentine Hemorrhagic Fever (AHF) is a serious endemic disease in Argentina, produced by Junin virus, whose host is the Sigmodontinae rodent Calomys musculinus. Within the endemic area, human incidence and proportion of infected rodents remains high for 5-10 years after the first appearance of the disease (epidemic [E] zone) and then gradually declines to sporadic cases (historic [H] zone). We tested the hypothesis that host populations within the E zone are large and well connected by gene flow, facilitating the transmission and maintenance of the virus, whereas those in the H and nonendemic (NE) zones are small and isolated, with the opposite effect. We estimated parameters affected by levels of gene flow and population size in 14 populations of C. musculinus: population effective size (Ne), genetic variability, and mean relatedness. Our hypothesis was not supported: the lowest levels of variability and of Ne and the highest genetic relatedness among individuals were found in the H zone. Populations from the NE zone displayed opposite results, whereas those in the E zone showed intermediate values. If we consider that populations are first NE, then E, and finally H, a correlative decrease in Ne was observed. Chronically infected females have a low reproductive success. We propose that this would lower Ne because each cohort would originate from a fraction of females of the previous generation, and affect other factors such as proportion of individuals that develop acute infection, probability of viral transmission, and evolution of virulence, which would explain, at least partly, the changing incidence of AHF.
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Genetic variability in the promoter region of TNF-α gene in the reservoir of Junin virus, Calomys musculinus (Rodentia, Cricetidae): Short communication
2017Co-Authors: Marina B. Chiappero, Imanol Cabaña, Gladys E. Calderón, Cristina N. GardenalAbstract:Abstract In this study, we assessed the genetic variability of the promoter region of TNF-α gene in three natural populations of the cricetid rodent Calomys musculinus . This species is the natural reservoir of Junin virus, the etiological agent of Argentine Hemorrhagic Fever. We found different levels of variability and varying signatures of natural selection in populations with different epidemiological histories.
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Differences in genetic structuring of populations of the Argentine Hemorrhagic Fever reservoir, the rodent Calomys musculinus , from endemic and non endemic zones
Julius-Kühn-Archiv, 2011Co-Authors: Marina B. Chiappero, Cristina N. Gardenal, C. Provensal, M. F. Piacenza, G. E. Calderón, Jaime PolopAbstract:We estimated the effective population size and genetic structuring within populations of the rodent reservoir of Argentine Hemorrhagic Fever, Calomys musculinus, from zones with different epidemiologic condition (non endemic, historic and epidemic). We found that populations from epidemic zones presented higher effective sizes, higher differentiation among subpopulations and higher levels of internal relatedness than in non-endemic zones. These results would explain the maintenance of the virus in populations from epidemic zones and the patchy distribution of infected rodents.
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Isolation and characterization of microsatellite markers in Calomys musculinus (Muridae, Sigmodontinae, Phyllotini), the natural reservoir of Junin virus
Molecular Ecology Notes, 2005Co-Authors: Marina B. Chiappero, Cristina N. Gardenal, Graciela M. Panzetta-dutariAbstract:Calomys musculinus, one of the most abundant rodent species in central Argentina, is the reservoir of Junin virus, the aetiological agent of Argentine Hemorrhagic Fever. We isolated six polymorphic microsatellite loci for microgeographical studies of population structure in this species. Amplification of these loci in 36 individuals from three natural populations revealed five to 14 alleles per locus and expected heterozygosities from 0.426 to 0.868. Cross-species amplifications suggest that primers designed for these loci may be useful in other closely related species of the tribe Phyllotini, but not in species of other more distantly related tribes of the subfamily Sigmodontinae.
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Inheritance of random amplified polymorphic DNA (RAPD-PCR) markers and their use in population genetic studies of Calomys musculinus (Rodentia, Muridae), the reservoir of Argentine Hemorrhagic Fever.
Hereditas, 2004Co-Authors: Marina B. Chiappero, Cristina N. GardenalAbstract:In order to assess the reliability of RAPD markers in the estimation of the genetic structure of natural populations of the murid rodent Calomys musculinus (reservoir of Junin virus, ethiological agent of Argentine Hemorrhagic Fever), we have analyzed the heritability of RAPD bands in 10 parents and their offspring (33 individuals). Fourteen out of a total of 119 bands obtained were absent in the parental patterns, but consistently amplified in offspring from some families. These bands can be eliminated from analyses. Overall degree of band sharing between individuals, including non-parental bands, correctly grouped members of a family in the same cluster in a UPGMA tree, with a high bootstrap percentage. Results support the usefulness of RAPDs as hereditable markers. One hundred polymorphic RAPD loci were identified in three natural populations of C. musculinus. Mean expected heterozygosity in three natural populations ranged from 0.206 to 0.220. Allele frequency based and phenotype based measures of genetic differentiation among natural populations of C. musculinus gave similar results (Weir and Cockerham's theta = 0.133; Excoffier et al.'s phi = 0.127). These values were considerably higher than those found previously using allozymes as genetic markers, and are compatible with moderate to low levels of gene flow among populations.
Cristina N. Gardenal - One of the best experts on this subject based on the ideXlab platform.
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contributions to the study of reservoirs of the Argentine Hemorrhagic Fever and hantavirus pulmonary syndrome
Biocell, 2021Co-Authors: Raul E Gonzalezittig, Gladys E. Calderón, Silvana Levis, P C Rivera, J D Pinotti, Natalia Ortiz, M L Martin, J Brignone, Cristina N. GardenalAbstract:In the context of COVID-19, we often ask ourselves what conditions favor the spread of zoonoses. Recent reviews point to its direct relationship with the decline in biodiversity due to habitat destruction or land use changes. When this occurs, some species become extinct, but those that survive and thrive, such as some rodents, are more likely to harbor pathogens that can affect humans. Our research focused on the study of molecular systematics and population genetic structure in rodent hosts of Mammarenavirus and Orthohantavirus affecting humans. From the analysis of phylogenetic relationships in Oligoryzomys and Calomys in South America, we were able to resolve contradictory taxonomic reports, obtaining the following rodent/viral genotype relationships in the endemic areas of Hantavirus pulmonary syndrome (HPS) in Argentina: Patagonia: O. longicaudatus/Andes;northwestern Argentina: O. occidentalis/Bermejo, O. chacoensis/Oran and C. fecundus/Laguna Negra;Misiones: O. nigripes/Juquitiba;Southern Litoral, Parana River Delta and the coast of the Uruguay River: O. flavescens/Lechiguanas and exceptionally, O. nigripes/Lechiguanas. We also detected the following rodent/mammarenavirus relationships: C. musculinus/Junin, C. venustus and C. fecundus/Latino-like. We observed that, in general, in conserved environments, the abundance of rodents was low although with high species diversity, while in places with greater disturbance, less diversity but a greater abundance of species transmitting zoonoses was found. It is not surprising then that the Argentine Hemorrhagic Fever endemic area is strongly associated with crops of the Humid Pampas and that HPS endemic areas are located in regions with high deforestation and introduction of crops or invasive exotic species. In times of pandemics, we should think about how diseases arise when our species advances over natural environments.
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Effective Population Size Differences in Calomys musculinus, the Host of Junín Virus: Their Relationship with the Epidemiological History of Argentine Hemorrhagic Fever.
The American journal of tropical medicine and hygiene, 2018Co-Authors: Marina B. Chiappero, Cristina N. Gardenal, Gladys E. Calderón, M. F. Piacenza, María C. Provensal, Jaime PolopAbstract:Argentine Hemorrhagic Fever (AHF) is a serious endemic disease in Argentina, produced by Junin virus, whose host is the Sigmodontinae rodent Calomys musculinus. Within the endemic area, human incidence and proportion of infected rodents remains high for 5-10 years after the first appearance of the disease (epidemic [E] zone) and then gradually declines to sporadic cases (historic [H] zone). We tested the hypothesis that host populations within the E zone are large and well connected by gene flow, facilitating the transmission and maintenance of the virus, whereas those in the H and nonendemic (NE) zones are small and isolated, with the opposite effect. We estimated parameters affected by levels of gene flow and population size in 14 populations of C. musculinus: population effective size (Ne), genetic variability, and mean relatedness. Our hypothesis was not supported: the lowest levels of variability and of Ne and the highest genetic relatedness among individuals were found in the H zone. Populations from the NE zone displayed opposite results, whereas those in the E zone showed intermediate values. If we consider that populations are first NE, then E, and finally H, a correlative decrease in Ne was observed. Chronically infected females have a low reproductive success. We propose that this would lower Ne because each cohort would originate from a fraction of females of the previous generation, and affect other factors such as proportion of individuals that develop acute infection, probability of viral transmission, and evolution of virulence, which would explain, at least partly, the changing incidence of AHF.
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Genetic variability in the promoter region of TNF-α gene in the reservoir of Junin virus, Calomys musculinus (Rodentia, Cricetidae): Short communication
2017Co-Authors: Marina B. Chiappero, Imanol Cabaña, Gladys E. Calderón, Cristina N. GardenalAbstract:Abstract In this study, we assessed the genetic variability of the promoter region of TNF-α gene in three natural populations of the cricetid rodent Calomys musculinus . This species is the natural reservoir of Junin virus, the etiological agent of Argentine Hemorrhagic Fever. We found different levels of variability and varying signatures of natural selection in populations with different epidemiological histories.
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Differences in genetic structuring of populations of the Argentine Hemorrhagic Fever reservoir, the rodent Calomys musculinus , from endemic and non endemic zones
Julius-Kühn-Archiv, 2011Co-Authors: Marina B. Chiappero, Cristina N. Gardenal, C. Provensal, M. F. Piacenza, G. E. Calderón, Jaime PolopAbstract:We estimated the effective population size and genetic structuring within populations of the rodent reservoir of Argentine Hemorrhagic Fever, Calomys musculinus, from zones with different epidemiologic condition (non endemic, historic and epidemic). We found that populations from epidemic zones presented higher effective sizes, higher differentiation among subpopulations and higher levels of internal relatedness than in non-endemic zones. These results would explain the maintenance of the virus in populations from epidemic zones and the patchy distribution of infected rodents.
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Isolation and characterization of microsatellite markers in Calomys musculinus (Muridae, Sigmodontinae, Phyllotini), the natural reservoir of Junin virus
Molecular Ecology Notes, 2005Co-Authors: Marina B. Chiappero, Cristina N. Gardenal, Graciela M. Panzetta-dutariAbstract:Calomys musculinus, one of the most abundant rodent species in central Argentina, is the reservoir of Junin virus, the aetiological agent of Argentine Hemorrhagic Fever. We isolated six polymorphic microsatellite loci for microgeographical studies of population structure in this species. Amplification of these loci in 36 individuals from three natural populations revealed five to 14 alleles per locus and expected heterozygosities from 0.426 to 0.868. Cross-species amplifications suggest that primers designed for these loci may be useful in other closely related species of the tribe Phyllotini, but not in species of other more distantly related tribes of the subfamily Sigmodontinae.
Julio I. Maiztegui - One of the best experts on this subject based on the ideXlab platform.
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From the Hematology and Immunology Sections, Instituto
2016Co-Authors: Felisa C Molinas, Julio I. Maiztegui, Maria M E De Bracco, De Investigaciones Medicos, Facultad De Medicina, Buenos Aires, The CentroAbstract:Coagulation studies were performed on samples taken from day 6 to day 22 after the onset of symptoms from 32 patients with Argentine Hemorrhagic Fever, grouped by clinical form into 17 mild cases, nine moderate cases, and six severe cases. The profiles of the coagulation factors during the course of disease were similar in all patients. Par-tial thromboplastin time activated with kaolin was prolonged in the early stages (78.0 ± 5.8 sec on day 6 and 47.5 ± 1.9 sec on day 14). Values for factors II and VII-X re-mained in the normal range, but factor V activity was greatly enhanced (257.6 % ± 54.7070 on day 10). Coagulation alterations tended to normalize after day 14. Fibrinogen profiles differed in the three clinical forms; on day 12 the fibrinogen level increased to 532 ± 39.3 mg/l00 ml in the moderate disease form and to 472 ± 40.9 mg/l00 ml in the severe form. Neither fibrin monomers nor fibrinogen degradation products were detected. Argentine Hemorrhagic Fever (AHF) is caused by infection with Junin virus [1]. This disease is characterized by hematologic and neurologi
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clinical case definitions for Argentine Hemorrhagic Fever
Clinical Infectious Diseases, 1999Co-Authors: Lee H Harrison, C J Peters, Kelly T Mckee, Ana M Briggiler, Maria R Feuillade, Julio Barrera G Oro, Neal A Halsey, Julio I. MaizteguiAbstract:Argentine Hemorrhagic Fever (AHF) is a potentially lethal infection in Argentina. The case-fatality ratio is >15%, but treatment reduces the mortality rate to <1%. Diagnosis is based on clinical and laboratory criteria, but no case definition has been validated. A chart review was conducted for patients hospitalized with suspected AHF. Individuals with a fourfold rise in antibody titer were classified as cases. The combination of a platelet count of <100,000/mm3 and a white blood cell (WBC) count of <2,500/mm3 had a sensitivity and specificity of 87% and 88%, respectively, thus suggesting that the use of these criteria in a case definition would be helpful for epidemiological studies of AHF. The combination of a platelet count of <100,000/mm3 and a WBC count of <4,000/mm3 had a sensitivity of 100% and a specificity of 71%; the use of these criteria in a case definition should be helpful for screening patients for therapy with immune plasma in the region where AHF is endemic.
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proinflammatory cytokines and elastase alpha 1 antitrypsin in Argentine Hemorrhagic Fever
American Journal of Tropical Medicine and Hygiene, 1999Co-Authors: R. F. Marta, Julio I. Maiztegui, V. S. Montero, C. E. Hack, A. Sturk, Felisa C MolinasAbstract:Argentine Hemorrhagic Fever (AHF) is a disease caused by Junin virus. In the acute phase, patients present hematologic and neurologic involvement with high levels of interferon-alpha and tumor necrosis factor-alpha (TNF-alpha. Nineteen patients with a confirmed diagnosis of AHF were studied: six severe, four moderate and nine mild cases. Serum levels of interleukin-6 (IL-6), IL-6 soluble receptor (IL-6sR), IL-8, IL-10, and elastase-alpha1-antitrypsin complex (E-alpha 1AT) were assayed by ELISAs. Levels of IL-6, IL-8, and IL-10 were high in nine, 12, and 13 patients, respectively, while levels of IL-6sR were high in two patients and low in one patient. Seven patients had increased levels of E-alpha1AT. Significant correlations were found between levels of both IL-8 and IL-10 with those of TNF-alpha as well as between IL-8 and E-alpha 1AT. These data demonstrate activation of pro-inflammatory and anti-inflammatory cytokine pathways, and statistical analysis showed differences among the clinical forms of illness. This study shows that IL-8 plays an essential role in neutrophil activation in AHF patients as demonstrated in other infectious diseases.
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protective efficacy of a live attenuated vaccine against Argentine Hemorrhagic Fever
The Journal of Infectious Diseases, 1998Co-Authors: Julio I. Maiztegui, Delia Enria, Silvana Levis, Kelly T Mckee, Ana M Briggiler, Maria R Feuillade, Julio Barrera G Oro, Lee H Harrison, Paul H Gibbs, Ana M. AmbrosioAbstract:Argentine Hemorrhagic Fever (AHF), caused by the arenavirus Junin, is a major public health problem among agricultural workers in Argentina. A prospective, randomized, double-blind, placebo-controlled, efficacy trial of Candid 1, a live attenuated Junin virus vaccine, was conducted over two consecutive epidemic seasons among 6500 male agricultural workers in the AHF-endemic region. Twenty-three men developed laboratory-confirmed AHF during the study; 22 received placebo and 1 received vaccine (vaccine efficacy 95%; 95% confidence interval [CI], 82%-99%). Three additional subjects in each group developed laboratory-confirmed Junin virus infection associated with mild illnesses that did not fulfill the clinical case definition for AHF, yielding a protective efficacy for prevention of any illness associated with Junin virus infection of 84% (95% CI, 60%-94%). No serious adverse events were attributed to vaccination. Candid 1, the first vaccine for the prevention of illness caused by an arenavirus, is safe and highly efficacious.
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early markers of blood coagulation and fibrinolysis activation in Argentine Hemorrhagic Fever
Thrombosis and Haemostasis, 1995Co-Authors: M V Heller, Julio I. Maiztegui, C. E. Hack, A. Sturk, Rosana F Marta, J W Cate, Felisa C MolinasAbstract:Junin virus, an arenaviridae, is the etiological agent of Argentine Hemorrhagic Fever. In addition to thrombocytopenia, patients present several alterations in both the blood coagulation and the fibrinolytic system, but diffuse intravascular coagulation could not be demonstrated. To investigate further the activation status of the two systems, levels of thrombin-antithrombin complexes (TAT), prothrombin fragment 1 + 2, protein C, total and free protein S, C4bBP, antithrombin III, t-PA, PAI-1 and D-dimer were measured. Fourteen patients with a confirmed diagnosis of Argentine Hemorrhagic Fever were included in the study, 2 were severe, 3 moderate and 9 mild clinical cases, but hemorrhages were slight throughout. Blood samples were collected for 6 consecutive days on admission and on remission. At admission TAT and F1 + 2 levels were increased in 13/14 patients, reaching 0.33 nM (0.06-0.87) and 2.16 nM (0.96-6.5), respectively. PC was low in 4 cases, fPS in 6 and tPS in 2, whereas C4bBP and ATIII values were within normal range. t-PA and D-dimer levels were high in 11/14 patients, reaching 20 ng/ml (2.7-106) and 1660 ng/ml (877-3780) respectively, while PAI-1 was considerably increased in the 2 severe cases and normal in the remainder. These results suggest low level though persistent process of blood coagulation and fibrinolysis activation in this viral Hemorrhagic disease. We believe these abnormalities may lead to the well described bleeding manifestations in these patients.
Delia Enria - One of the best experts on this subject based on the ideXlab platform.
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quali quantitative study of the social variables defining transmission scenarios of Argentine Hemorrhagic Fever in the provinces of buenos aires and santa fe 2001 2010
Salud Colectiva, 2014Co-Authors: Andrea Veronica Mastrangelo, Paula Tagliabue, Lorena Berro, Dario De Carolis, Anabel Sinchi, Clara Digilio, Delia EnriaAbstract:The aim of this paper was to characterize transmission scenarios of Argentine Hemorrhagic Fever in the post-vaccination period (2001-2010). The study was made up of three phases. The first consisted of a quantitative analysis using the database of the Dr. Julio I. Maiztegui National Institute of Human Viral Diseases [Instituto Nacional de Enfermedades Virales Humanas] regarding the confirmed cases in the period of study (221 cases). Taking into account the transmission site and the known endemic area, cases were grouped into three hypothetical transmission scenarios, identified as: a) classical, b) emerging-reemerging, c) traveling. In the second phase, in order to test these hypotheses, in-depth interviews were carried out from August to September 2011 within an intentionally selected sample of patients distributed proportionally among the three hypotheses. Finally, in the third stage, the data obtained for each hypothetical scenario were grouped into three spatiotemporal scales: the microscale (subject), the mesoscale (locality) and macroscale (region). The results show that new transmission sites are associated with the social dynamics of cereal production and port-bound routes.
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treatment of Argentine Hemorrhagic Fever
Antiviral Research, 2008Co-Authors: Delia Enria, Ana M Briggiler, Zaida SanchezAbstract:Argentine Hemorrhagic Fever (AHF) is a rodent-borne illness caused by the arenavirus Junin that is endemic to the humid pampas of Argentina. AHF has had significant morbidity since its emergence in the 1950s, with a case-fatality rate of the illness without treatment between 15% and 30%. The use of a live attenuated vaccine has markedly reduced the incidence of AHF. Present specific therapy involves the transfusion of immune plasma in defined doses of neutralizing antibodies during the prodromal phase of illness. However, alternative forms of treatment are called for due to current difficulties in early detection of AHF, related to its decrease in incidence, troubles in maintaining adequate stocks of immune plasma, and the absence of effective therapies for severely ill patients that progress to a neurologic-Hemorrhagic phase. Ribavirin might be a substitute for immune plasma, provided that the supply is guaranteed. Immune immunoglobulin or monoclonal antibodies should also be considered. New therapeutic options such as those being developed for systemic inflammatory syndromes should also be valuated in severe forms of AHF.
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Evaluation of an enzyme-linked immunosorbent assay for detection of antibodies to Junin virus in rodents.
Journal of virological methods, 2002Co-Authors: María Alejandra Morales, Delia Enria, Gladys E. Calderón, Ana M. Ambrosio, Laura M Riera, Marta S. SabattiniAbstract:Junin virus is the etiological agent of Argentine Hemorrhagic Fever, a serious rodent-borne disease. An enzyme-linked immunosorbent assay (ELISA) to detect Junin virus IgG antibodies in rodents was evaluated using sera from 27 Calomys musculinus and five Calomys laucha, inoculated experimentally with a live attenuated strain of this arenavirus. The test performance was compared against an indirect immunofluorescence assay (IFA). The ELISA had a sensitivity and specificity of 100% and a reproducibility of 87.9% for samples with titers above the selected cut-off value. IFA had lower sensitivity (53%) with the same specificity. The ELISA results were similar, whether carried out on whole blood or serum samples, thus eliminating the need for serum separation. A high correlation (K=0.86) between ELISA and IFA results was obtained from 1011 wild sigmodontine and murine rodents collected within and outside of the Argentine Hemorrhagic Fever endemic area. These results indicate that Junin virus IgG ELISA is the most suitable assay for detection of Junin virus antibodies in rodent samples.
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relationship between hematopoietic growth factors levels and hematological parameters in Argentine Hemorrhagic Fever
American Journal of Hematology, 2000Co-Authors: Rosana F Marta, Delia Enria, Felisa C MolinasAbstract:Argentine Hemorrhagic Fever (AHF) is a viral disease caused by Junin virus and characterized by hematologic and neurological involvement. The main hematologic features are leukopenia, thrombocytopenia, and bone marrow hypoplasia. Hematopoietic growth factors serum levels were measured by ELISA technique in forty-eight patients with confirmed diagnosis of AHF. Patients were classified according to the clinical picture in 15 severe (SCF), 17 moderate (MoCF), and 16 mild (MiCF) cases. Erythropoietin levels were decreased in 28 of 45 patients and raised in 4 SCF patients. Twenty-four of 38 patients had high G-CSF levels at admittance in accordance with clinical picture severity, while IL-3, GM-CSF, and TGF-β were normal in most cases. A direct correlation was found between G-CSF and TNF-α levels. Thrombopoietin levels were found to be raised in 19 of 21 patients. In conclusion, the low levels of Epo may contribute to the severe bone marrow erythroblastopenia described in AHF patients, while G-CSF seems to be a marker of illness severity. Am. J. Hematol. 64:1–6, 2000. © 2000 Wiley-Liss, Inc.
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protective efficacy of a live attenuated vaccine against Argentine Hemorrhagic Fever
The Journal of Infectious Diseases, 1998Co-Authors: Julio I. Maiztegui, Delia Enria, Silvana Levis, Kelly T Mckee, Ana M Briggiler, Maria R Feuillade, Julio Barrera G Oro, Lee H Harrison, Paul H Gibbs, Ana M. AmbrosioAbstract:Argentine Hemorrhagic Fever (AHF), caused by the arenavirus Junin, is a major public health problem among agricultural workers in Argentina. A prospective, randomized, double-blind, placebo-controlled, efficacy trial of Candid 1, a live attenuated Junin virus vaccine, was conducted over two consecutive epidemic seasons among 6500 male agricultural workers in the AHF-endemic region. Twenty-three men developed laboratory-confirmed AHF during the study; 22 received placebo and 1 received vaccine (vaccine efficacy 95%; 95% confidence interval [CI], 82%-99%). Three additional subjects in each group developed laboratory-confirmed Junin virus infection associated with mild illnesses that did not fulfill the clinical case definition for AHF, yielding a protective efficacy for prevention of any illness associated with Junin virus infection of 84% (95% CI, 60%-94%). No serious adverse events were attributed to vaccination. Candid 1, the first vaccine for the prevention of illness caused by an arenavirus, is safe and highly efficacious.