Enfoque Rápido en Contexto Comunitario (ERCC): evaluando las medidas preventivas para Hantavirus en la Comarca Andina Patagónica desde la perspectiva de la participación comunitaria / Rapid Approach in Community Context (ERCC): evaluating preventive measures for Hantavirus in the Andean Patagonian Region from the perspective of community participation

Introducción: la creciente preocupación por eventos epidémicos de origen zoonótico generó la necesidad de estrategias integrales que corrigiesen la baja adaptabilidad y tensiones que se generan al implementar acciones de orden jerárquico superior en el contexto comunitario. Con el objeto de explicar un Enfoque Rápido en Contexto Comunitario (ERCC), este trabajo se propone evaluar dentro del contexto de un programa de salud pública la participación comunitaria en la prevención del Hantavirus en la Comarca Andina del Paralelo 42. Metodología: El presente ERCC utilizó visitas y observaciones al sitio, entrevistas cara a cara y grupales, precedidas por una revisión documental de la literatura. La información se recopiló en un corto período de tiempo y el análisis se utilizó para desarrollar recomendaciones informadas para los tomadores de decisiones de salud pública. Resultados: Se observo que cada comunidad enfrenta desafíos más allá del hantavirus y es esencial que epidemiólogos, prestadores de servicios asistenciales y municipalidades trabajen más estrechamente con la población local para prevenir y manejar mejor cualquier brote de enfermedad. Se pudieron identificar 6 recomendaciones que le permitirían a las comunidades un mejor manejo de futuros brotes con un enfoque participativo. Conclusiones: El ERCC es una intervención rápida y discreta que puede ser llevada a cabo por un pequeño equipo con una interferencia mínima en la comunidad. El ERCC también podría ser adaptado por las autoridades de salud pública a muchos contextos diferentes, incluso con grupos vulnerables, para ayudar a que la promoción y la prevención sean más relevantes y efectivas a nivel local (AU)

Introduction: the growing concern for epidemic events of zoonotic origin generated the need for comprehensive strategies that correct the low adaptability and tensions generated when implementing actions of higher hierarchical order in the community context. In order to explain a Rapid Approach in Community Context (ERCC), this paper aims to evaluate within the context of a public health program community participation in the prevention of Hantavirus in the Andean Region of the 42nd Parallel. Methodology: The present ERCC used site visits and observations, face-to-face and group interviews, preceded by a documentary review of the literature. The information was collected over a short period of time and the analysis was used to develop informed recommendations for public health decision makers. Results: It was observed that each community faces challenges beyond hantavirus and it is essential that epidemiologists, care providers and municipalities work more closely with the local population to better prevent and manage any disease outbreak. We were able to identify 6 recommendations that would allow communities to better manage future outbreaks with a participatory approach. Conclusions: The ERCC is a rapid and discreet intervention that can be carried out by a small team with minimal interference in the community. The ERCC could also be adapted by public health authorities to many different contexts, including with vulnerable groups, to help make promotion and prevention more relevant and effective at the local level (AU)

Production and Purification of Hantavirus Glycoproteins in Drosophila melanogaster S2 Cells.

Hantaviruses, are rodent-borne viruses found worldwide that are transmitted to humans through inhalation of contaminated excreta. They can cause a renal or a pulmonary syndrome, depending on the virus, and no effective treatment is currently available for either of these diseases. Hantaviral particles are covered by a protein lattice composed of two glycoproteins (Gn and Gc) that mediate adsorption to target cells and fusion with endosomal membranes, making them prime targets for neutralizing antibodies. Here we present the methodology to produce soluble recombinant glycoproteins in different conformations, either alone or as a stabilized Gn/Gc complex, using stably transfected Drosophila S2 cells.

Modulations in the host cell proteome by the hantavirus nucleocapsid protein.

Hantaviruses have evolved a unique translation strategy to boost the translation of viral mRNA in infected cells. Hantavirus nucleocapsid protein (NP) binds to the viral mRNA 5' UTR and the 40S ribosomal subunit via the ribosomal protein S19. NP associated ribosomes are selectively loaded on viral transcripts to boost their translation. Here we demonstrate that NP expression upregulated the steady-state levels of a subset of host cell factors primarily involved in protein processing in the endoplasmic reticulum. Detailed investigation of Valosin-containing protein (VCP/p97), one of the upregulated host factors, in both transfected and virus infected cells revealed that NP with the assistance of VCP mRNA 5' UTR facilitates the translation of downstream VCP ORF. The VCP mRNA contains a 5' UTR of 987 nucleotides harboring six unusual start codons upstream of the correct start codon for VCP which is located at 988th position from the 5' cap. In vitro translation of a GFP reporter transcript harboring the VCP mRNA 5' UTR generated both GFP and a short polypeptide of ~14 KDa by translation initiation from start codon located in the 5' UTR at 542nd position from the 5' cap. The translation initiation from 542nd AUG in the UTR sequence was confirmed in cells using a dual reporter construct expressing mCherry and GFP. The synthesis of 14KDa polypeptide dramatically inhibited the translation of the ORF from the downstream correct start codon at 988th position from the 5' cap. We report that purified NP binds to the VCP mRNA 5' UTR with high affinity and NP binding site is located close to the 542ndAUG. NP binding shuts down the translation of 14KDa polypeptide which then facilitates the translation initiation at the correct AUG codon. Knockdown of VCP generated lower levels of poorly infectious hantavirus particle in the cellular cytoplasm whose egress was dramatically inhibited in human umbilical vein endothelial cells. We demonstrated that VCP binds to the hantavirus glycoprotein Gn before its incorporation into assembled virions and facilitates viral spread to neighboring cells during infection. Our results suggest that ribosome engagement at the 542nd AUG codon in the 5' UTR likely regulates the endogenous steady state levels of VCP in cells. Hantaviruses interrupt this regulatory mechanism to enhance the steady state levels of VCP in virus infected cells. This augmentation facilitates virus replication, supports the transmission of the virus to adjacent cells, and promotes the release of infectious virus particles from the host cell.

Direct and indirect effects of Puumala hantavirus on platelet function.

Thrombocytopenia is a cardinal symptom of hantavirus-induced diseases including Puumala virus (PUUV)-induced hemorrhagic fever with renal syndrome (HFRS), which is associated with impaired platelet function, bleeding manifestations and augmented thrombotic risk. However, the underlying mechanisms causing thrombocytopenia and platelet hypo-responsiveness are unknown. Thus, we investigated the direct and indirect impact of PUUV on platelet production, function and degradation. Analysis of PUUV-HFRS patient blood revealed that platelet hypo-responsiveness in PUUV infection was cell-intrinsic and accompanied by reduced platelet-leukocyte aggregates (PLAs) and upregulation of monocyte tissue factor (TF), whereas platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation was comparable to healthy controls. Plasma CXCL4 levels followed platelet count dynamics throughout disease course. PUUV activated both neutrophils and monocytes in vitro, but platelet desialylation, degranulation and GPIIb/IIIa activation as well as PLA formation and endothelial adhesion under flow remained unaltered in the presence of PUUV. Further, MEG-01 megakaryocytes infected with PUUV displayed unaltered polyploidization, expression of surface receptors and platelet production. However, infection of endothelial cells with PUUV significantly increased platelet sequestration. Our data thus demonstrate that although platelet production, activation or degradation are not directly modulated, PUUV indirectly fosters thrombocytopenia by sequestration of platelets to infected endothelium. Upregulation of immunothrombotic processes in PUUV-HFRS may further contribute to platelet dysfunction and consumption. Given the pathophysiologic similarities of hantavirus infections, our findings thus provide important insights into the mechanisms underlying thrombocytopenia and highlight immune-mediated coagulopathy as potential therapeutic target.

Assessing Pulmonary Epithelial Damage in Hantavirus Cardiopulmonary Syndrome: Challenging the Predominant Role of Vascular Endothelium through sRAGE as a Potential Biomarker.

Hantavirus cardiopulmonary syndrome (HCPS) is a severe respiratory illness primarily associated with microvascular endothelial changes, particularly in the lungs. However, the role of the pulmonary epithelium in HCPS pathogenesis remains unclear. This study explores the potential of soluble Receptors for Advanced Glycation End-products (sRAGE) as a biomarker for assessing pulmonary epithelial damage in severe HCPS, challenging the prevailing view that endothelial dysfunction is the sole driver of this syndrome. We conducted a cross-sectional study on critically ill HCPS patients, categorizing them into mild HCPS, severe HCPS, and negative control groups. Plasma sRAGE levels were measured, revealing significant differences between the severe HCPS group and controls. Our findings suggest that sRAGE holds promise as an indicator of pulmonary epithelial injury in HCPS and may aid in tracking disease progression and guiding therapeutic strategies. This study brings clarity on the importance of investigating the pulmonary epithelium's role in HCPS pathogenesis, offering potential avenues for enhanced diagnostic precision and support in this critical public health concern.

Differences in the Susceptibility of Human Tubular Epithelial Cells for Infection with Orthohantaviruses.

Diseases induced by infection with pathogenic orthohantaviruses are characterized by a pronounced organ-specific manifestation. Pathogenic Eurasian orthohantaviruses cause hemorrhagic fever with renal syndrome (HFRS) with often massive proteinuria. Therefore, the use of a relevant kidney cell culture would be favorable to analyze the underlying cellular mechanisms of orthohantavirus-induced acute kidney injury (AKI). We tested different human tubular epithelial cell lines for their suitability as an in vitro infection model. Permissiveness and replication kinetics of highly pathogenic Hantaan virus (HTNV) and non-/low-pathogenic Tula virus (TULV) were analyzed in tubular epithelial cell lines and compared to human primary tubular epithelial cells. Ana-lysis of the cell line HK-2 revealed the same results for viral replication, morphological and functional effects as observed for HTNV in primary cells. In contrast, the cell lines RPTEC/TERT1 and TH1 demonstrated only poor infection rates after inoculation with HTNV and are unusable as an infection model. While pathogenic HNTV infects primary tubular and HK-2 cells, non-/low-pathogenic TULV infects neither primary tubular cells nor the cell line HK-2. Our results show that permissiveness of renal cells varies between orthohantaviruses with differences in pathogenicity and that HK-2 cells demonstrate a suitable in vitro model to study viral tropism and pathogenesis of orthohantavirus-induced AKI.

Favorable course of leptospirosis and hantavirus-induced acute tubulointerstitial nephritis under corticosteroid treatment.

BACKGROUND: We present two children with acute tubulointerstitial nephritis (ATIN) caused by leptospirosis in a 12-year-old boy and hantavirus in a 10-year-old girl. The role of glucocorticoids in the management of ATIN triggered by infectious agents is unclear. CASE-DIAGNOSIS/TREATMENT: Both children were hospitalized with jaundice, elevated serum creatinine, and thrombocytopenia. There was no oliguria or hypertension. Urine analysis revealed tubular proteinuria. Kidney biopsy was performed on one patient and showed tubulointerstitial inflammation with mild mesangial proliferation. Both patients were treated with glucocorticoids in view of deteriorating kidney function with respective serum creatinine values of 5.2 and 4.1 mg/dl. Both children exhibited an excellent clinical and biochemical response to treatment. Neither of the patients required dialysis. Positive serology test results indicated a recent leptospirosis and hantavirus infection. CONCLUSIONS: Leptospirosis and hantavirus associated ATIN share common clinical and biochemical features. Due to the low incidence in Europe these infectious causes of kidney dysfunction may be overlooked. Glucocorticoids may be considered in the management of ATIN.

Aplicación de la Teoría del Cuidado Cultural a la investigación: prácticas de cuidado preventivas de hantavirus / Applying Cultural Care Theory to research: hantavirus preventive care practices

INTRODUCCIÓN: La investigación en enfermería surge de las necesidades y experiencias en la práctica y debe contribuir a generar, redefinir y actualizar el conocimiento de enfermería a través de comprobación o generación de nuevas teorías de enfermería. El conocimiento nuevo generado o actualizado debe retornar y mejorar la práctica del cuidado de enfermería dirigido las personas, familia y comunidad. Sin embargo en ocasiones la interrelación investigación y teoría no es clara, afectando de esta manera la relevancia de la aplicación de las teorías de enfermería en la práctica del cuidado de enfermería. OBJETIVO: La presente reflexión responde al objetivo de ejemplificar cómo se aplicó la Teoría del Cuidado Cultural Universalidad y Diversidad de Leininger al estudio del fenómeno de las prácticas de cuidado preventivas de hantavirus. DESARROLLO: Sistematización crítica de la experiencia investigativa a través de una propuesta metodológica, que describe cómo la Teoría del Cuidado Cultural Universalidad y Diversidad de Leininger guio el proceso de investigación sobre las prácticas de cuidado preventivas de hantavirus, factores personales, sociales, modos de vida y creencias culturales. CONCLUSIONES: Un elemento fundamental en toda investigación de enfermería es mostrar de manera clara y explícita cómo la teoría se interconecta con todas las fases de la investigación y en consecuencia genera conocimiento de enfermería para la práctica del cuidado.

INTRODUCTION: Nursing research arises from needs and experiences in practice and should contribute to generate, redefine and update nursing knowledge by testing or developing new nursing theories. Such new or updated knowledge should lead to improvements in the practice of nursing care applied to persons, family, and community. However, sometimes the interrelationship between research and theory is unclear, affecting the relevance of such theories to nursing care practice. OBJECTIVE: The present reflection aims to exemplify how Leininger's Theory of Cultural Care Universality and Diversity was applied to the study of hantavirus preventive care practices. DEVELOPMENT: Critical systematization of the research experience through a proposed methodology that describes how Leininger's Theory of Cultural Care Universality and Diversity guided research related to hantavirus preventive practices, personal and social factors, lifestyles, and cultural beliefs. CONCLUSIONS: A fundamental element in all nursing research is to clearly and explicitly show how theory interfaces with all phases of research and consequently generates nursing knowledge for caring practice.

Diagnostico Serológico de Hantavirus en el Departamento de La Paz, Bolivia, en la gestión 2022 / Serological diagnosis of Hantavirus in the department of La Paz, Bolivia in the 2022 management

INTRODUCCIÓN: el síndrome pulmonar por hantavirus (SPHV) es una enfermedad viral aguda causada por miembros del género Orthohantavirus, familia Bunyaviridae transmitida por roedores presente en zonas tropicales y semitropicales del departamento de La Paz. OBJETIVOS: diagnosticar hantavirus por serología IgG e IgM, en el noreste del Departamento de La Paz, Bolivia, en pacientes con sospecha de infección por Hantavirus mediante la prueba de ELISA y realizar un análisis epidemiológico básico. MATERIALES Y MÉTODOS: este trabajo es un estudio de tipo transversal descriptivo, se utilizó el método de diagnóstico ELISA (Euroinmun) para detectar la presencia de anticuerpos inmunoglobulina M (IgM) e inmunoglobulina G(IgG) para hantavirus en muestras de suero, con un universo de 138 muestras de Enero a Agosto de la gestión 2022 en pacientes con sospecha de infección por Hantavirus enviadas de distintos hospitales y centros de salud al Laboratorio de Virología del Instituto Nacional de Laboratorios en Salud (INLASA). RESULTADOS Y CONCLUSIONES: se detectó presencia de IgM e IgG para hantavirus en las muestras de suero procesadas por serología en el Laboratorio de Virología, de las cuales de 138 muestras, un 12% son positivas para IgG, 4% positivos para IgM y el 84%, restante es negativo. Estas muestras provienen de centros y establecimientos de salud del noreste del Departamento de La Paz, observándose un mayor porcentaje de casos en el sexo masculino afectando al grupo etario de 41 a 50 años y existiendo un número elevado de casos presentes entre los meses de febrero y abril, además de observar signos y síntomas registradas en fichas epidemiológicas.

INTRODUCTION: Hantavirus pulmonary syndrome (SPHV) is an acute viral disease caused by members of the genus Orthohantavirus, family Bunyaviridae, transmitted by rodents present in tropical and semitropical areas of the department of La Paz. OBJECTIVES: diagnose hantavirus by IgG and IgM serology, in the northeast of the Department of La Paz, Bolivia, in patients with suspected Hantavirus infection using the ELISA test and perform a basic epidemiological analysis. MATERUAKS AND METHODS: this work is a descriptive cross-sectional study, the ELISA (Euroimmun) diagnostic method was used to detect the presence of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies to hantavirus in serum samples, with a universe of 138 samples. from January to August of the 2022 management in patients with suspected Hantavirus infection sent from different hospitals and health centers to the Virology Laboratory of the National Institute of Health Laboratories (INLASA). RESULTS AND CONCLUSIONS: the presence of IgM and IgG for hantavirus was detected in the serum samples processed by serology in the Virology Laboratory, of which 138 samples, 12% are positive for IgG, 4% positive for IgM and the remaining 84% are negative. These samples come from health centers and establishments in the northeast of the Department of La Paz, observing a higher percentage of cases in the male sex, affecting the age group of 41 to 50 years, and there being a high number of cases present between the months of February and April, in addition to observing signs and symptoms recorded in epidemiological files.

A rare case of acute acalculous cholecystitis secondary to hantavirus infection with renal syndrome.

Hantaviruses are single-stranded RNA viruses. They are transmitted to humans by rodents and insectivore hosts. Some Hantavirus subtypes are the causative agents of haemorrhagic fever with renal syndrome (HFRS), which is characterized by fever, thrombocytopenia, and acute kidney injury. Hantavirus infection is difficult to diagnose due to its non-specific clinical symptoms. Causes of acalculous cholecystitis are severe trauma or burn, surgery, long-term starvation and some viral infections. It is very rare for Hantavirus to cause acute acalculous cholecystitis. The treatment of acute acalculous cholecystitis is usually directed towards its symptoms. A 22-year-old male forest worker was admitted to our emergency outpatient clinic with the complaints of fatigue, oliguria, fever, abdominal pain and vomiting. After the clinical and laboratory examinations, HFRS and acute cholecystitis secondary to Hantavirus infection were diagnosed. The patient's condition and clinical findings improved after supportive treatment. Hantavirus infection should be considered in patients with acute kidney injury, cholecystitis and thrombocytopenia (Fig. 2, Ref. 10). Keywords: Hantavirus, acute kidney injury, acalculous cholecystitis, thrombocytopeni.

Central nervous system infection with Seoul Orthohantavirus in a child after hematopoietic stem cell transplantation: a case report.

BACKGROUND: Patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT) are prone to complicate viral infection. Central nervous system (CNS) involvement caused by the viruses is rare but with poor prognosis. Hantavirus, which usually cause hemorrhagic fever with renal syndrome (HFRS), and none case has been reported about these infection in allo-HSCT patients. CASE PRESENTATION: In August 2021, a 13-year-old male child developed intermittent fever and refractory hypotension after allo-HSCT. Magnetic resonance imaging of the head revealed abnormal signal foci in the left midbrain cerebral peduncle and bilateral thalamus. His family reported traces of mouse activity in the patient's home kitchen. HFRS was suspected, but with no significant kidney damage. The specific immunoglobulin (Ig) G and M of hantavirus were negative. The metagenomic next-generation sequencing (mNGS) detected Seoul Orthohantavirus (SEOV) sequences directly in cerebrospinal fluid and blood. CONCLUSIONS: Allo-HSCT patients are a high-risk group for infection. Usually the causative agent of infection is difficult to determine, and sometimes the site of infection is concealed. This report highlights the importance of suspecting hantavirus infection in allo-HSCT patients with CNS symptoms despite the absence of renal syndromes. The mNGS is a powerful tool for detecting pathogens. CNS infection with Seoul orthohantavirus in transplant patients is rare but possible as demonstrated in this case. To the best of our knowledge, this is the first reported case employing mNGS to diagnose SEOV caused CNS infection in an allo-HSCT patient.

Modelamiento del síndrome cardiopulmonar por hantavirus / Modeling of hantavirus cardiopulmonary syndrome

INTRODUCCIÓN: El síndrome cardiopulmonar por hantavirus es una enfermedad causada por un virus perteneciente al orden bunyanvirales, y transmitida hacia los humanos a través de roedores. Esta enfermedad en Chile es considerada endémica, la cual tiene una alta tasa de letalidad. En la actualidad existen estudios que evidencian el contagio entre personas del virus Andes, cuya localidad se concentra en los países de Argentina y Chile. OBJETIVOS: Analizar la posibilidad de transmisión de hantavirus entre humanos, mediante un modelo matemático tipo SEIR. MÉTODOS: Se plantea un modelo matemático tipo SEIR (susceptible, expuesto, infeccioso y recuperado) para expresar la dinámica de la enfermedad por hantavirus, incluyendo la posibilidad de transmisión entre humanos y la percepción del riesgo. Resultados: El máximo de contagio entre humanos disminuye cerca de 25% tras aumentar la percepción de riesgo de las personas, mediante la reducción de la tasa de resistencia al cambio y aumento la velocidad de reaccionar de las personas. CONCLUSIONES: Es urgente revisar las estrategias de comunicación de riesgo y medidas de prevención ante esta posibilidad de contagios masivos entre humanos, además de fortalecer la investigación y proyectar el desarrollo de una vacuna para proteger las poblaciones expuestas a esta enfermedad con alta tasa de letalidad.

INTRODUCTION: Hantavirus cardiopulmonary syndrome is an infection caused by rodents of the Bunyanvirales family towards humans. This disease in Chile is considered endemic, which has a high fatality rate. At present, some studies show the contagion between people of the Andes virus, whose locality is concentrated in Argentina and Chile. OBJECTIVES: Analyze the possibility of hantavirus transmission between humans using an SEIR-type mathematical model. METHODS: An SEIR (Susceptible, Exposed, Infectious and Recovered) mathematical model to express the dynamics of hantavirus disease is proposed, including the possibility of human-to-human transmission and the perception of risk. RESULTS: The peak of human-to-human contagion decreases by about 25% after increasing people's perception of risk by reducing the rate of resistance to changeand increasing the speed of people's reaction. CONCLUSIONS: It is urgent to review risk communication strategies and prevention measures in the face of this possibility of massive human-tohuman infections, in addition to strengthening research and planning the development of a vaccine to protect populations exposed to this disease with a high fatality rate.

Alcohol Consumption and Its Influence on the Clinical Picture of Puumala Hantavirus Infection.

Puumala hantavirus (PUUV) causes hemorrhagic fever with renal syndrome. Characteristic clinical findings include acute kidney injury (AKI), thrombocytopenia, and capillary leakage. Smoking increases the risk of severe AKI, but it is not known whether alcohol consumption predisposes patients to a more severe infection. Liver and pancreatic enzymes, as well as biomarkers of alcohol consumption (gamma-glutamyl transferase, GGT; carbohydrate-deficient transferrin, CDT; GGT-CDT combination; and ethyl glucuronide, EtG), were measured from 66 patients with acute PUUV infection during hospitalization and at the convalescence phase. Alcohol consumption was present in 41% of the study population, 15% showing signs of heavy drinking. Alcohol use did not affect the severity of PUUV induced AKI nor the overall clinical picture of the infection. Liver enzyme levels (GGT or alanine aminotransferase, ALT) were elevated in 64% of the patients, but the levels did not associate with the markers reflecting the severity of the disease. Serum amylase activities at the convalescent stage were higher than those at the acute phase (p < 0.001). No cases with acute pancreatitis were found. In conclusion, our findings indicate that alcohol consumption does not seem to affect the clinical course of an acute PUUV infection.

Diseño y validación de un cuestionario para medir prácticas preventivas de hantavirus en una comunidad endémica / Design and validation of a questionnaire to measure hantavirus preventive practices in an endemic community

RESUMEN Objetivo. Diseñar y analizar las evidencias de validez de contenido, estructura interna y fiabilidad de un cuestionario de prácticas preventivas de hantavirus en una comunidad endémica en el contexto panameño. Materiales y métodos. Estudio cuantitativo de diseño instrumental. Esta investigación se desarrolló en cuatro etapas: revisión de literatura, validez de contenido a través de juicio de expertos con el método de agregados individuales y el cálculo de la V de Aiken; prueba piloto y validación psicométrica, a través del análisis factorial exploratorio (AFE) y análisis de fiabilidad de las puntuaciones del instrumento con el alfa ordinal. Resultados. Se evidenció validez de contenido y se reportó valores de V de Aiken superiores a 0,70 en el límite inferior del intervalo de confianza al 95%. En la estructura interna se identificó que los 8 ítems subyacen a un solo factor que explica el 60,70% de la varianza total de la prueba y con cargas factoriales superiores a 0,40; en el análisis de fiabilidad se obtuvo un valor de alfa ordinal de 0,84, valor considerado como bueno. Conclusiones. El cuestionario de práctica preventivas de hantavirus es un instrumento breve que muestra propiedades psicométricas aceptables para medir las actividades o conductas que realizan las personas para prevenir el hantavirus.

ABSTRACT Objective. To design and analyze the evidence of content validity, internal structure, and reliability of a questionnaire of preventive practices for hantavirus in an endemic community in the Panamanian context. Material and methods. Quantitative study of instrumental design. This research was conducted in four phases: Literature review, content validity through expert judgment with the individual aggregate method and the calculation of the V Aiken, pilot test and psychometric validation, through exploratory factor analysis (EFA) and reliability analysis of instrument scores with ordinal alpha. Results. Content validity was evidenced and V Aiken values higher than 0.70 were reported in the lower limit of 95% CI. In the internal structure we identified that the 8 items underlie a single factor that explains 60.70% of the total variance of the test and with factor loadings greater than 0.40; during the reliability analysis, we obtained an ordinal alpha value of 0.84, which is considered good. Conclusions. The Hantavirus preventive practical questionnaire is a brief instrument that shows acceptable psychometric properties to measure the activities or behaviors that people carry out to prevent hantavirus.

Novel infection of pericytes by Andes virus enhances endothelial cell permeability.

Andes Virus (ANDV) non-lytically infects pulmonary microvascular endothelial cells (PMECs) causing a severe capillary leak syndrome termed Hantavirus Pulmonary Syndrome (HPS). Basolaterally, PMECs are in contact with pericytes which play critical roles in regulating PMEC permeability and immune cell recruitment. We discovered that ANDV persistently infects primary human vascular pericytes for up to 9 days, and that PMEC monolayer permeability was increased by supernatants from ANDV-infected pericytes. Pericyte-directed PMEC permeability was consistent with the high-level secretion of the permeability factor VEGF (vascular endothelial growth factor) elicited by ANDV-infected pericytes. These findings suggest that ANDV infection of pericytes augments PMEC permeability and reveal a novel mechanism of pericyte-directed vascular barrier dysfunction that contributes to HPS and provides new therapeutic targets.

Hantavirus Research in Finland: Highlights and Perspectives.

Finland has the highest incidence of hantavirus infections globally, with a significant impact on public health. The large coverage of boreal forests and the cyclic dynamics of the dominant forest rodent species, the bank vole Myodes glareolus, explain most of this. We review the relationships between Puumala hantavirus (PUUV), its host rodent, and the hantavirus disease, nephropathia epidemica (NE), in Finland. We describe the history of NE and its diagnostic research in Finland, the seasonal and multiannual cyclic dynamics of PUUV in bank voles impacting human epidemiology, and we compare our northern epidemiological patterns with those in temperate Europe. The long survival of PUUV outside the host and the life-long shedding of PUUV by the bank voles are highlighted. In humans, the infection has unique features in pathobiology but rarely long-term consequences. NE is affected by specific host genetics and risk behavior (smoking), and certain biomarkers can predict the outcome. Unlike many other hantaviruses, PUUV causes a relatively mild disease and is rarely fatal. Reinfections do not exist. Antiviral therapy is complicated by the fact that when symptoms appear, the patient already has a generalized infection. Blocking vascular leakage measures counteracting pathobiology, offer a real therapeutic approach.

Controversias sobre el uso de corticoides en el síndrome cardiopulmonar por hantavirus / Controversies on corticosteroid therapy in hantavirus cardiopulmonary syndrome

Resumen El síndrome cardiopulmonar por hantavirus es una zoonosis emergente en la Argentina, que presenta baja incidencia, pero elevada mortalidad. No existe tratamiento farmacológico especifico y la única alternativa actual es la terapia de apoyo. En este artículo se expone la patogenia del síndrome cardiopulmonar por hantavirus a través de la revisión de las experiencias clínicas de otros países de Sudamérica, en particular Chile, y la adquirida en el Hospital de Infecciosas Francisco Javier Muñiz de Buenos Aires, Argentina. Se discute sobre la administración temprana de corticoides en este síndrome, teniendo en cuenta que la evidencia a favor de su uso es insuficiente.

Abstract Hantavirus cardiopulmonary syndrome is an emerging zoonosis in Argentina, which has low incidence but high death rates. No specific pharmacological therapy is available and symptomatic therapy is the only current alterna tive. This article presents the pathogenesis of hantavirus cardiopulmonary syndrome through a review of clinical experiences in neighbor South American countries, mainly Chile, and the experience acquired at the Infectious Diseases Hospital Francisco Javier Muñiz, Buenos Aires, Argentina. The role of early corticosteroid therapy is discussed taking into account that there is insufficient evidence favoring its use in the hantavirus cardiopulmonary syndrome.

Prediction model to discriminate leptospirosis from hantavirus

SUMMARY OBJECTIVE: The aim of this study was to build a prediction model to discriminate precociously hantavirus infection from leptospirosis, identifying the conditions and risk factors associated with these diseases. METHODS: A logistic regression model in which the response variable was the presence of hantavirus or leptospirosis was adjusted. RESULTS: As a result, the method selected the following variables that influenced the prediction formula: sociodemographic variables, clinical manifestations, and exposure to environmental risks. All variables considered in the model presented statistical significance with a p<0.05 value. The accuracy of the model to differentiate hantavirus from leptospirosis was 88.7%. CONCLUSIONS: Concluding that the development of statistical tools with high potential to predict the disease, and thus differentiate them precociously, can reduce hospital costs, speed up the patient's care, reduce morbidity and mortality, and assist health professionals and public managers in decision-making.

Amycolatopsis dendrobii sp. nov., an endophytic actinomycete isolated from Dendrobium heterocarpum Lindl.

Three novel actinomycete strains, designated as DR6-1T, DR6-2 and DR6-4, isolated from the roots of Dendrobium heterocarpum Lindl in Thailand were studied using a polyphasic taxonomic approach. The strains grew at 20-37 °C, at pH 5-10 and with 5 % (w/v) NaCl. They contained meso-diaminopimelic acid in the cell-wall peptidoglycan and MK-9(H4) was a major menaquinone. Arabinose and galactose were the major sugars in the cell wall. The predominant cellular fatty acids were iso-C16 : 0 and iso-C15 : 0. The detected polar lipids were diphosphatidylglycerol, hydroxyphosphatidylethanolamine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylglycerol. Strains DR6-1T, DR6-2 and DR6-4 shared 99.9-100 % 16S rRNA gene sequence similarity and were closely related to Amycolatopsis echigonensis JCM 21831T (98.7-98.8%). The approximate genome size of strain DR6-1T was 9.6 Mb with a G+C content of 69.6 mol%. The ANIb and dDDH values between genomic sequences of strain DR6-1T and Amycolatopsis echigonensis JCM21831T, Amycolatopsis rubida JCM 10871T and Amycolatopsis nivea KCTC 39515T were 90.55, 92.25, 92.60%, and 47.20, 52.10 and 52.50%, respectively. Based on the phenotypic, chemotaxonomic and genotypic characteristics, it has been concluded that strains DR6-1T, DR6-2 and DR6-4 represent a novel species of the genus Amycolatopsis for which the name Amycolatopsis dendrobii sp. nov. is proposed. The type strain is DR6-1T (=JCM 33742T=KCTC 49546T=TISTR 2840T).

Binding of the Andes Virus Nucleocapsid Protein to RhoGDI Induces the Release and Activation of the Permeability Factor RhoA.

Andes virus (ANDV) nonlytically infects pulmonary microvascular endothelial cells (PMECs), causing acute pulmonary edema termed hantavirus pulmonary syndrome (HPS). In HPS patients, virtually every PMEC is infected; however, the mechanism by which ANDV induces vascular permeability and edema remains to be resolved. The ANDV nucleocapsid (N) protein activates the GTPase RhoA in primary human PMECs, causing VE-cadherin internalization from adherens junctions and PMEC permeability. We found that ANDV N protein failed to bind RhoA but coprecipitates RhoGDI (Rho GDP dissociation inhibitor), the primary RhoA repressor that normally sequesters RhoA in an inactive state. ANDV N protein selectively binds the RhoGDI C terminus (residues 69 to 204) but fails to form ternary complexes with RhoA or inhibit RhoA binding to the RhoGDI N terminus (residues 1 to 69). However, we found that ANDV N protein uniquely inhibits RhoA binding to an S34D phosphomimetic RhoGDI mutant. Hypoxia and vascular endothelial growth factor (VEGF) increase RhoA-induced PMEC permeability by directing protein kinase Cα (PKCα) phosphorylation of S34 on RhoGDI. Collectively, ANDV N protein alone activates RhoA by sequestering and reducing RhoGDI available to suppress RhoA. In response to hypoxia and VEGF-activated PKCα, ANDV N protein additionally directs the release of RhoA from S34-phosphorylated RhoGDI, synergistically activating RhoA and PMEC permeability. These findings reveal a fundamental edemagenic mechanism that permits ANDV to amplify PMEC permeability in hypoxic HPS patients. Our results rationalize therapeutically targeting PKCα and opposing protein kinase A (PKA) pathways that control RhoGDI phosphorylation as a means of resolving ANDV-induced capillary permeability, edema, and HPS. IMPORTANCE HPS-causing hantaviruses infect pulmonary endothelial cells (ECs), causing vascular leakage, pulmonary edema, and a 35% fatal acute respiratory distress syndrome (ARDS). Hantaviruses do not lyse or disrupt the endothelium but dysregulate normal EC barrier functions and increase hypoxia-directed permeability. Our findings reveal a novel underlying mechanism of EC permeability resulting from ANDV N protein binding to RhoGDI, a regulatory protein that normally maintains edemagenic RhoA in an inactive state and inhibits EC permeability. ANDV N sequesters RhoGDI and enhances the release of RhoA from S34-phosphorylated RhoGDI. These findings indicate that ANDV N induces the release of RhoA from PKC-phosphorylated RhoGDI, synergistically enhancing hypoxia-directed RhoA activation and PMEC permeability. Our data suggest inhibiting PKC and activating PKA phosphorylation of RhoGDI as mechanisms of inhibiting ANDV-directed EC permeability and therapeutically restricting edema in HPS patients. These findings may be broadly applicable to other causes of ARDS.