Person-to-Person Transmission of Andes Virus

Epidemiologic and genetic data show that person-to-person spread likely took place during the prodromal phase or shortly after it ended

First Evidence of Akodon-Borne Orthohantavirus in Northeastern Argentina

Orthohantaviruses (genus Orthohantavirus, family Hantaviridae) are the etiologic agents of Hantavirus Pulmonary Syndrome in the Americas. In South America, orthohantaviruses are highly diverse and are hosted by sigmodontine rodents (subfamiliy Sigmodontinae, family Cricetidae), an also diverse group of rodents. The aims of this work were to (1) identify orthohantavirus hosts and (2) to study the spatial and temporal variations in the prevalence of infection and their associations with community, environmental and individual characteristics, in different environments of Misiones province, northeastern Argentina. Live-capture sessions were carried out during two years in different land uses, with a trapping effort of 31,653 trap nights. We captured 719 individuals from the species Akodon montensis, Rattus rattus, Mus musculus, Calomys tener, Thaptomys nigrita, Oligoryzomys nigripes, Euryoryzomys russatus, Oligoryzomys flavescens, Brucepattersonius sp., and Juliomys pictipes. Antibodies against orthohantavirus were detected in Akodon montensis in one natural protected and one periurban areas, and it was the most abundant species in almost every study sites. We observed the presence of spatial focality of orthohantavirus infection and a positive association with host abundance suggesting the existence of a threshold density. At the individual level, large, reproductively active, and male individuals were more likely to have antibodies against orthohantavirus. This is the first record of orthohantavirus infection in A. montensis in Argentina, which shows the importance of investigations about emerging diseases.Fil: Burgos, Eliana Florencia. Administracion Nacional de Laboratorios E Institutos de Salud "dr. Carlos G. Malbran". Instituto Nacional de Medicina Tropical.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vadell, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Administracion Nacional de Laboratorios E Institutos de Salud "dr. Carlos G. Malbran". Instituto Nacional de Medicina Tropical.; ArgentinaFil: Bellomo, Carla María. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; ArgentinaFil: Martinez, Valeria Paula. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; ArgentinaFil: Salomón, Oscar Daniel. Administracion Nacional de Laboratorios E Institutos de Salud "dr. Carlos G. Malbran". Instituto Nacional de Medicina Tropical.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gomez Villafañe, Isabel Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentin

Hantavirus Pulmonary Syndrome in Tucumán province associated to an unexpected viral genotype

We describe the characterization of the viral genotype involved in the first case of hantavirus pul-monary syndrome reported in Tucumán, a Northwestern province of Argentina. A 23-year-old woman, with no record of travel history and previously diagnosed with an antiphospholipid syndrome, died after 11 days of severe cardiopulmonary insufficiency. Among the four endemic regions of hantavirus pulmonary syndrome in Argentina, the Northwest Region has the highest incidence, exceeding 50% of all reported cases in the country. Until now, only Salta and Jujuy (2 out of the 6 provinces composing the Northwest Region), reported cases of hantavirus pulmonary syndrome, all of which occurred in the Yungas Forest area. Remarkably, the viral genotype characterized in this case showed higher nucleotide identity with the Andes-BsAs genotype most prevalent in Buenos Aires province, located 1400 km apart from Tucumán, than with any of the commonly found genotypes in the Northwest Region. The Andes-BsAs genotype has been associated with 30% lethality and interhuman transmission in Buenos Aires province. Interhuman transmission cannot be ruled out in the present case.Fil: Ciancaglini, Matías. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; ArgentinaFil: Bellomo, Carla María. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; ArgentinaFil: Torres Cabrero Clara. Hospital Italiano; ArgentinaFil: Alonso Daniel. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; ArgentinaFil: Bassi, Sabrina Cecilia. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Iglesias, Ayelén Aluminé. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martinez, Valeria Paula. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; Argentin

Ampliación de la distribución del Orthohantavirus genotipo Pergamino: Primer registro en la Provincia de Entre Ríos, Argentina

Hantavirus Pulmonary Syndrome (HPS) is an emerging infectious disease of the Americas. Eight native rodent species have been identified as HPS virus reservoirs in Argentina. The aim of this work was to detect the orthohantavirus genotypes present in a rodent community that inhabits a zone where a fatal HPS case occurred within an endemic locality of Central Argentina. We captured 27 rodents with a trapping effort of 723 trap nights. We detected 14.3% of infected Akodon azarae with the Pergamino genotype. This result expands the known distribution of this orthohantavirus. Although the Pergamino genotype has not been associated with human cases, the information about its distribution is relevant for risk assessment against potential changes in the virus infectivity.El síndrome pulmonar por hantavirus (SPH) es una enfermedad infecciosa emergente en América. Ocho especies de roedores nativos han sido identificadas como reservorios del virus causante del SPH en la Argentina. El objetivo de este trabajo fue detectar los genotipos de orthohantavirus presentes en una comunidad de roedores que habita en una zona donde ocurrió un caso fatal de SPH, en una localidad endémica de Argentina central. Se capturaron 27 individuos con un esfuerzo de 723 trampas-noche. Se detectó un 14,3% de Akodon azarae infectados con el genotipo pergamino. Este resultado amplía el conocido rango de distribución de este orthohantavirus. A pesar de que el genotipo pergamino no ha sido asociado con casos humanos hasta el momento, la información sobre su distribución es relevante para analizar el riesgo ante un potencial cambio en la infectividad del virus.Fil: Gomez Villafañe, Isabel Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución; ArgentinaFil: Burgos, Eliana Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Medicina Tropical; ArgentinaFil: Coelho, Rocío María. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; ArgentinaFil: Bellomo, Carla María. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; ArgentinaFil: Garcilazo Amatti, Jerónimo. Ministerio de Salud de la Nación. Dirección de Epidemiología; ArgentinaFil: Martinez, Valeria Paula. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentin

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

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.Peer reviewe

Hantavirus in rodents of Buenos Aires Province: are seroprevalence and abundance related?

Oligoryzomys flavescens and Akodon azarae are two rodent species living in agroecosystems of the Pampean region. O. flavescens is a reservoir of the Lechiguanas genotype, associated with Hantavirus Pulmonary Syndrome, whereas Akodon azarae is a reservoir of the Pergamino genotype, which has not been associated with human cases. Our objective was to evaluate whether there is a relationship between abundance and seroprevalence in both rodent species, as this may help to identify situations of high risk of exposure to hantavirus for humans. Eleven longitudinal rodent capture-mark-recapture surveys were conducted in three railway embankments in agricultural landscapes (Exaltación de la Cruz Departament, Buenos Aires province, Argentina), from 2014 through 2016. The trapping effort was 1800 trap-nights per survey. During these surveys, demographic data and blood samples were collected. Blood samples were analyzed by means of ELISAs to determine the presence of hantavirus-specific antibodies. For each rodent species, the relationship between seroprevalence and its abundance was assessed through logit-linked binomial generalized linear models using the number of infected individuals by sampling session as the response variable (i.e., successees, with the corresponding number of tested blood samples per group as trials). Models containing the species’ MNA as a predictor and the null models were evaluated. Using a multi-model approach, averaged parameters and their relative importance were calculated using Akaike weights (AIC). The main finding in this work was that both A. azarae and O. flavescens exhibit a negative relationship between prevalence and abundance. A possible explanation for this result is that populations reach their smaller numbers when these consist mainly of overwintering adults, which had longer exposures with higher chances of becoming infected, whereas larger populations are observed soon after the reproductive season, when new recruits are unlikely to be infected yet. Thus, the effect of prevalence and abundance on the risk of human exposure could be compensatory. This suggests that there would be no particular season of increased risk; prevention and surveillance should be permanent.Para acceder a la videoconferencia completa, hacer clic en "Enlace externo".Sociedad Latinoamericana de Ecología de Vectore

The Tumor-Specific Expression of L1 Retrotransposons Independently Correlates with Time to Relapse in Hormone-Negative Breast Cancer Patients

Background: Long-Interspersed Nuclear Element (L1) retrotransposons are silenced in healthy tissues but unrepressed in cancer. Even if L1 reactivation has been associated with reduced overall survival in breast cancer (BC) patients, a comprehensive correlation with clinicopathological features is still missing. Methods: Using quantitative, reverse-transcription PCR, we assessed L1 mRNA expression in 12 BC cells, 210 BC patients and in 47 normal mammary tissues. L1 expression was then correlated with molecular and clinicopathological data. Results: We identified a tumor-exclusive expression of L1s, absent in normal mammary cells and tissues. A positive correlation between L1 expression and tumor dedifferentiation, lymph-node involvement and increased immune infiltration was detected. Molecular subtyping highlighted an enrichment of L1s in basal-like cells and cancers. By exploring disease-free survival, we identified L1 overexpression as an independent biomarker for patients with a high risk of recurrence in hormone-receptor-negative BCs. Conclusions: Overall, L1 reactivation identified BCs with aggressive features and patients with a worse clinical fate

Hantavirus infection-induced B cell activation elevates free light chains levels in circulation

In humans, orthohantaviruses can cause hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). An earlier study reported that acute Andes virus HPS caused a massive and transient elevation in the number of circulating plasmablasts with specificity towards both viral and host antigens suggestive of polyclonal B cell activation. Immunoglobulins (Igs), produced by different B cell populations, comprise heavy and light chains; however, a certain amount of free light chains (FLCs) is constantly present in serum. Upregulation of FLCs, especially clonal species, associates with renal pathogenesis by fibril or deposit formations affecting the glomeruli, induction of epithelial cell disorders, or cast formation in the tubular network. We report that acute orthohantavirus infection increases the level of Ig FLCs in serum of both HFRS and HPS patients, and that the increase correlates with the severity of acute kidney injury in HFRS. The fact that the kappa to lambda FLC ratio in the sera of HFRS and HPS patients remained within the normal range suggests polyclonal B cell activation rather than proliferation of a single B cell clone. HFRS patients demonstrated increased urinary excretion of FLCs, and we found plasma cell infiltration in archival patient kidney biopsies that we speculate to contribute to the observed FLC excreta. Analysis of hospitalized HFRS patients' peripheral blood mononuclear cells showed elevated plasmablast levels, a fraction of which stained positive for Puumala virus antigen. Furthermore, B cells isolated from healthy donors were susceptible to Puumala virus in vitro, and the virus infection induced increased production of Igs and FLCs. The findings propose that hantaviruses directly activate B cells, and that the ensuing intense production of polyclonal Igs and FLCs may contribute to acute hantavirus infection-associated pathological findings. Author summary Orthohantaviruses are globally spread zoonotic pathogens, which can cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) with significant burden to human health. The pathogenesis mechanisms of orthohantavirus-caused diseases are not known in detail; however, excessive immune response towards the virus with concomitant pathological effects against host tissues appears to be a contributing factor. Here we report an increase of free immunoglobulin (Ig) light chains (FLCs), components required to make complete Ig molecules, in blood of acute HFRS and HPS. Samples collected during acute HFRS demonstrated increased FLCs levels in the urine and blood of patients hospitalized due the disease. Furthermore, the FLC levels positively correlated with markers of acute kidney injury. In addition, our results show that orthohantaviruses can infect and activate B cells to produce FLCs as well as whole Igs, which provides a mechanistic explanation of the increased FLC levels in patients. Taken together, our results suggest that aberrant antibody responses might play a role in the pathogenesis of orthantavirus infections.Peer reviewe

Epidemiological description, case-fatality rate, and trends of Hantavirus Pulmonary Syndrome: 9 years of surveillance in Argentina

Hantavirus pulmonary syndrome (HPS) is an endemic disease in Argentina, one of the most affected countries in the Americas. Andes virus (ANDV) is the main Orthohantavirus species causing HPS in Argentina. In this study, the geographical distribution, clinical presentation, and epidemiological features of HPS from all endemic regions of Argentina were analyzed. We focused on the clinical and epidemiological data from 533 HPS cases confirmed during the period 2009 to 2017 by the National Reference Laboratory for Hantavirus. A case-fatality rate of 21.4% was registered, and most of the cases presented a severe clinical picture requiring intensive care treatment (84%). Since HPS first detection in 1995 the case-fatality rate showed a general trend towards a decrease. After more than 22 years of experience in HPS diagnosis and surveillance, we discuss some possible factors implicated in this tendency. This clinical and epidemiological analysis gives a global perspective, being useful to detect trends and patterns, to update preventive actions at a national level, and evaluate their impact on public health.Fil: Alonso, Daniel Oscar. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio E Instituto de Salud "Dr. C. G. Malbran". Departamento Virus; ArgentinaFil: Iglesias, Ayelén Aluminé. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio E Instituto de Salud "Dr. C. G. Malbran". Departamento Virus; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Coelho, Rocío María. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio E Instituto de Salud "Dr. C. G. Malbran". Departamento Virus; ArgentinaFil: Periolo, Natalia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio E Instituto de Salud "Dr. C. G. Malbran". Departamento Virus; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bruno, Agostina. Hospital San Vicente de Paul; ArgentinaFil: Córdoba, Maria Teresa. Hospital San Vicente de Paul; ArgentinaFil: Filomarino, Noemi. Hospital Señor Del Milagro; ArgentinaFil: Quipildor, Marcelo. Hospital San Vicente de Paul; ArgentinaFil: Biondo, Emiliano. Ministerio de Salud de la Provincia de Chubut; ArgentinaFil: Fortunato, Eduardo. Provincia de Buenos Aires. Ministerio de Salud; ArgentinaFil: Bellomo, Carla María. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio E Instituto de Salud "Dr. C. G. Malbran". Departamento Virus; ArgentinaFil: Martínez, Valeria Paula. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio E Instituto de Salud "Dr. C. G. Malbran". Departamento Virus; Argentin