RESUMO
Dengue is a significant health problem due to the high burden of critical infections during outbreaks. In 1997, the World Health Organization (WHO) classified dengue as dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). It was revised in 2009 (updated in 2015), and the new guidelines recommended classifying patients as dengue without warning signs (DNS), dengue with warning signs (DWS), and severe dengue (SD). Although the utility of the revised 2009 classification for clinical studies is accepted, for immunological studies it needs to be clarified. We determined the usefulness of the 2009 classification for pediatric studies that analyze the circulating interleukin (IL)-6 and IL-8, two inflammatory cytokines. Plasma levels of IL-6 and IL-8 were evaluated in the acute and convalescent phases by flow cytometry in children with dengue classified using the 1997 and 2009 WHO guidelines. The plasma levels of IL-6 and IL-8 were elevated during the acute and decreased during convalescence, and both cytokines served as a good marker of acute dengue illness compared to convalescence. There were no differences in the plasma level of the evaluated cytokines among children with different clinical severity with any classification, except for the IL-8, which was higher in DWS than DNS. Based on the levels of IL-8, the 2009 classification identified DWS plus SD (hospital-treated children) compared to the DNS group [area under the curve (AUC): 0.7, p = 0.028]. These results support the utility of the revised 2009 (updated in 2015) classification in studies of immune markers in pediatric dengue.
Assuntos
Dengue , Interleucina-6 , Interleucina-8 , Organização Mundial da Saúde , Humanos , Dengue/imunologia , Dengue/diagnóstico , Criança , Masculino , Feminino , Interleucina-6/sangue , Pré-Escolar , Interleucina-8/sangue , Dengue Grave/diagnóstico , Dengue Grave/imunologia , Dengue Grave/sangue , Adolescente , Índice de Gravidade de Doença , Biomarcadores/sangue , Vírus da Dengue/imunologia , Guias de Prática Clínica como Assunto , Citometria de Fluxo , Lactente , Citocinas/sangueRESUMO
Viral hemorrhagic fever poses a significant public health challenge due to its severe clinical presentation and high mortality rate. The diagnostic process is hindered by similarity of symptoms across different diseases and the broad spectrum of pathogens that can cause hemorrhagic fever. In this study, we applied viral metagenomic analysis to 43 serum samples collected by the Public Health Laboratory (Fundação Ezequiel Dias, FUNED) in Minas Gerais State, Brazil, from patients diagnosed with hemorrhagic fever who had tested negative for the standard local hemorrhagic disease testing panel. This panel includes tests for Dengue virus (DENV) IgM, Zika virus IgM, Chikungunya virus IgM, yellow fever IgM, Hantavirus IgM, Rickettsia rickettsii IgM/IgG, and Leptospira interrogans IgM, in addition to respective molecular tests for these infectious agents. The samples were grouped into 18 pools according to geographic origin and analyzed through next-generation sequencing on the NextSeq 2000 platform. Bioinformatic analysis revealed a prevalent occurrence of commensal viruses across all pools, but, notably, a significant number of reads corresponding to the DENV serotype 2 were identified in one specific pool. Further verification via real-time PCR confirmed the presence of DENV-2 RNA in an index case involving an oncology patient with hemorrhagic fever who had initially tested negative for anti-DENV IgM antibodies, thereby excluding this sample from initial molecular testing. The complete DENV-2 genome isolated from this patient was taxonomically classified within the cosmopolitan genotype that was recently introduced into Brazil. These findings highlight the critical role of considering the patient's clinical condition when deciding upon the most appropriate testing procedures. Additionally, this study showcases the potential of viral metagenomics in pinpointing the viral agents behind hemorrhagic diseases. Future research is needed to assess the practicality of incorporating metagenomics into standard viral diagnostic protocols.
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Brazilian mammarenavirus, or Sabiá virus (SABV), is a New World (NW) arenavirus associated with fulminant hemorrhagic disease in humans and the sole biosafety level 4 microorganism ever isolated in Brazil. Since the isolation of SABV in the 1990s, studies on viral biology have been scarce, with no available countermeasures against SABV infection or disease. Here we provide a comprehensive review of SABV biology, including key aspects of SABV replication, and comparisons with related Old World and NW arenaviruses. SABV is most likely a rodent-borne virus, transmitted to humans, through exposure to urine and feces in peri-urban areas. Using protein structure prediction methods and alignments, we analyzed shared and unique features of SABV proteins (GPC, NP, Z, and L) that could be explored in search of therapeutic strategies, including repurposing intended application against arenaviruses. Highly conserved catalytic activities present in L protein could be targeted for broad-acting antiviral activity among arenaviruses, while protein-protein interactions, such as those between L and the matrix protein Z, have evolved in NW arenaviruses and should be specific to SABV. The nucleoprotein (NP) also shares targetable interaction interfaces with L and Z and exhibits exonuclease activity in the C-terminal domain, which may be involved in multiple aspects of SABV replication. Envelope glycoproteins GP1 and GP2 have been explored in the development of promising cross-reactive neutralizing antibodies and vaccines, some of which could be repurposed for SABV. GP1 remains a challenging target in SABV as evolutive pressures render it the most variable viral protein in terms of both sequence and structure, while antiviral strategies targeting the Z protein remain to be validated. In conclusion, the prediction and analysis of protein structures should revolutionize research on viruses such as SABV by facilitating the rational design of countermeasures while reducing dependence on sophisticated laboratory infrastructure for experimental validation.
Assuntos
Infecções por Arenaviridae , Arenavirus do Novo Mundo , Humanos , Proteínas Virais/genética , Infecções por Arenaviridae/prevenção & controle , Antivirais , Biologia MolecularRESUMO
There is no specific chemotherapy approved for the treatment of pathogenic arenaviruses that cause severe hemorrhagic fever (HF) in the population of endemic regions in America and Africa. The present study reports the effects of the natural flavonoid quercetin (QUER) on the infection of A549 and Vero cells with Junín virus (JUNV), agent of the Argentine HF. By infectivity assays, a very effective dose-dependent reduction of JUNV multiplication was shown by cell pretreatment at 2-6 h prior to the infection at non-cytotoxic concentrations, with 50% effective concentration values in the range of 6.1-7.5 µg/mL. QUER was also active by post-infection treatment but with minor efficacy. Mechanistic studies indicated that QUER mainly affected the early steps of virus adsorption and internalization in the multiplication cycle of JUNV. Treatment with QUER blocked the phosphorylation of Akt without changes in the total protein expression, detected by Western blot, and the consequent perturbation of the PI3K/Akt pathway was also associated with the fluorescence redistribution from membrane to cytoplasm of TfR1, the cell receptor recognized by JUNV. Then, it appears that the cellular antiviral state, induced by QUER treatment, leads to the prevention of JUNV entry into the cell.
Assuntos
Infecções por Arenaviridae , Arenavirus , Chlorocebus aethiops , Animais , Quercetina/farmacologia , Flavonoides , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Células VeroRESUMO
Resumen Presentamos el caso de una mujer de 38 años sin antecedentes personales relevantes, residente de Ciudad Autónoma de Buenos Aires, que consultó por fiebre, cefalea retroocular mialgias, ar tralgias y exantema maculopapular pruriginoso en dorso de manos y pies de 6 días de evolución. El laboratorio presentaba linfopenia, trombocitopenia grave y hepatitis anictérica. El cónyuge había cursado internación tres semanas antes por un cuadro de similares características sin diagnóstico etiológico. Posteriormente, la paciente evolucionó con metrorragia y petequias axilares asociados a fotofobia, somnolencia y temblor fino de la lengua, con líquido cefalorraquídeo normal, cumpliendo tratamiento con ceftriaxona 2 g/día intravenoso por 7 días. La tomografía computarizada de abdomen y pelvis evidenciaba un hematoma de pared abdominal izquierdo. Se derivaron muestras serológicas al Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui para virus dengue, leptospirosis y hantavirus con resultados no reactivos y RT-PCR de virus Junín que resultó positiva. Retrospectivamente se realizó el diagnóstico del cónyuge por detección de anticuerpos IgG para virus Junín por ELISA y prueba de neutralización. Ninguno de los dos casos presentaba un nexo epidemiológico claro. Nuestro objetivo es remarcar la importancia de la sospecha clínica fuera de áreas endémicas.
Abstract We present the case of a 38-year-old woman with no relevant medical history, resident of the City of Buenos Aires, who was admitted in hospital for presenting fever, retroocular headache, myalgia, arthralgia, and maculopapular pruritic rash on the back of the hands and feet of 6 days of evolution. Laboratory tests revealed lymphopenia, severe thrombocytopenia, and anicteric hepatitis. Her husband had been hospitalized three weeks earlier for a condition of similar characteristics without etiological diagnosis. Subsequently, it evolved with metrorrhagia and axillary petechiae associated with photophobia, drowsiness, and fine tremor of the tongue with normal cerebrospinal fluid, treated with intravenous ceftriaxone 2 g/day for 7 days. Computed tomography of abdomen and pelvis showed a left abdominal wall hematoma. Serological samples were sent to the National Institute of Human Viral Diseases Dr. Julio I. Maiztegui for dengue virus, leptospirosis and hantavirus with non-reactive results, and RT-PCR of Junín virus that was positive. Retrospectively, the spouse was diagnosed by detection of IgG antibodies to Junin virus by ELISA and neutralization tests. Neither of the two cases had a clear epidemiological link. Our aim is to highlight the importance of clinical suspicion outside of endemic areas.
RESUMO
Junín virus (JUNV), a member of the family Arenaviridae, is the etiological agent of the Argentine hemorrhagic fever, an endemic disease in the rural region of Argentina lacking a specific chemotherapy. Aryl hydrocarbon receptor (AHR) is expressed in several mammalian tissues and has been indicated as a sensor of ligands from variable sources and a modulator of the cell immune response. Interestingly, recent studies have suggested that the activation or depression of the AHR signaling pathway may play a role in the outcome of diverse human viral infections. In the present report, the effect of the pharmacological modulation of AHR on JUNV in vitro infection was analyzed. An initial microarray screening showed that the AHR pathway was overexpressed in JUNV-infected hepatic cells. Concomitantly, the infection of Vero and Huh-7 cells with the JUNV strains IV4454 and Candid#1 was significantly inhibited in a dose-dependent manner by treatment with CH223191, a specific AHR antagonist, as detected by infectivity assays, real-time RT-PCR and immunofluorescence detection of viral proteins. Furthermore, the pro-viral role of AHR in JUNV infection appears to be independent of the IFN-I pathway. Our findings support the promising perspectives of the pharmacological modulation of AHR as a potential target for the control of AHF.
Assuntos
Arenaviridae , Vírus Junin , Animais , Humanos , Argentina , Mamíferos , Receptores de Hidrocarboneto Arílico/genética , Transdução de Sinais , Replicação ViralRESUMO
We present the case of a 38-year-old woman with no relevant medical history, resident of the City of Buenos Aires, who was admitted in hospital for presenting fever, retroocular headache, myalgia, arthralgia, and maculopapular pruritic rash on the back of the hands and feet of 6 days of evolution. Laboratory tests revealed lymphopenia, severe thrombocytopenia, and anicteric hepatitis. Her husband had been hospitalized three weeks earlier for a condition of similar characteristics without etiological diagnosis. Subsequently, it evolved with metrorrhagia and axillary petechiae associated with photophobia, drowsiness, and fine tremor of the tongue with normal cerebrospinal fluid, treated with intravenous ceftriaxone 2 g/day for 7 days. Computed tomography of abdomen and pelvis showed a left abdominal wall hematoma. Serological samples were sent to the National Institute of Human Viral Diseases Dr. Julio I. Maiztegui for dengue virus, leptospirosis and hantavirus with non-reactive results, and RT-PCR of Junín virus that was positive. Retrospectively, the spouse was diagnosed by detection of IgG antibodies to Junin virus by ELISA and neutralization tests. Neither of the two cases had a clear epidemiological link. Our aim is to highlight the importance of clinical suspicion outside of endemic areas.
Presentamos el caso de una mujer de 38 años sin antecedentes personales relevantes, residente de Ciudad Autónoma de Buenos Aires, que consultó por fiebre, cefalea retroocular mialgias, artralgias y exantema maculopapular pruriginoso en dorso de manos y pies de 6 días de evolución. El laboratorio presentaba linfopenia, trombocitopenia grave y hepatitis anictérica. El cónyuge había cursado internación tres semanas antes por un cuadro de similares características sin diagnóstico etiológico. Posteriormente, la paciente evolucionó con metrorragia y petequias axilares asociados a fotofobia, somnolencia y temblor fino de la lengua, con líquido cefalorraquídeo normal, cumpliendo tratamiento con ceftriaxona 2 g/día intravenoso por 7 días. La tomografía computarizada de abdomen y pelvis evidenciaba un hematoma de pared abdominal izquierdo. Se derivaron muestras serológicas al Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui para virus dengue, leptospirosis y hantavirus con resultados no reactivos y RT-PCR de virus Junín que resultó positiva. Retrospectivamente se realizó el diagnóstico del cónyuge por detección de anticuerpos IgG para virus Junín por ELISA y prueba de neutralización. Ninguno de los dos casos presentaba un nexo epidemiológico claro. Nuestro objetivo es remarcar la importancia de la sospecha clínica fuera de áreas endémicas.
Assuntos
Febre Hemorrágica Americana , Humanos , Feminino , Adulto , Estudos Retrospectivos , FebreRESUMO
Rodents are very important organisms within ecosystems; however, some species are considered pests because they consume and damage crops and because they are vectors, hosts, or reservoirs in the transmission of emerging infectious diseases. Rodents in Bolivia are represented by 148 species, Oligoryzomys microtis (Allen, 1916) being a species of public health importance because it is considered a potential natural reservoir of the Chapare virus, which causes Chapare Hemorrhagic Fever, and it is a deadly disease for humans. Its impact on public health is still unknown. The present study consisted of recording the presence of the species O. microtis through the use of Sherman-type live capture traps for small mammals arranged in linear transects in the wild and intervened habitats of the Samuzabety community, where the Chapare virus was detected for the first time, this community is located in the Chapare Province of the department of Cochabamba, Bolivia. The species recorded were the rodents Oligoryzomys microtis (morphotype matogrossae), Proechimys brevicauda, Neacomys vargasllosai, Hylaeamys perenensis, and the marsupial Metachiurus nudicaudatus. The presence of the species O. microtis (morphotype matogrossae) in the community of Samuzabety is confirmed. This species is associated with forest habitats with nearby and surrounding crops. The species O. microtis has epidemiological relevance as it is the natural reservoir of the Río Mamoré Hantavirus and is currently considered a potential reservoir of the Chapare virus and other Arenaviruses.
Los roedores son organismos muy importantes dentro de los ecosistemas; sin embargo, algunas especies son consideradas como plagas porque consumen y dañan cultivos y porque son vectores, hospederos o reservorios en la trasmisión de enfermedades infecciosas emergentes. Los roedores en Bolivia están representados por 148 especies, entre las cuales Oligoryzomys microtis (Allen, 1916) es una especie de importancia en salud pública, debido a que es considerada como potencial reservorio natural del virus Chapare, el cual produce la fiebre hemorrágica Chapare, enfermedad mortal para el ser humano y con un impacto en la salud pública aún desconocido. En este estudio se registró la presencia de la especie O. microtis?/i>, mediante el uso de trampas de captura viva tipo Sherman para pequeños mamíferos dispuestas en transectos lineales, en los hábitats silvestres e intervenidos de la comunidad de Samuzabety, sitio en el que se detectó por primera vez el virus Chapare. Esta comunidad se encuentra ubicada en la Provincia Chapare del departamento de Cochabamba, Bolivia. Las especies registradas fueron los roedores Oligoryzomys microtis (morfotipo matogrossae), Proechimys brevicauda, Neacomys vargasllosai, Hylaeamys perenensis y el marsupial Metachiurus nudicaudatus. Se confirma la presencia de la especie O. microtis (morfotipo matogrossae) en la comunidad de Samuzabety, la cual se encuentra asociada con hábitats de bosques, con cultivos cercanos y a su alrededor. La especie O. microtis tiene relevancia epidemiológica al ser el reservorio natural del hantavirus Río Mamoré y al ser considerado actualmente como potencial reservorio del virus Chapare y de otros arenavirus.
RESUMO
Hemorrhagic fever viruses (HFVs) pose a threat to global public health owing to the emergence and re-emergence of highly fatal diseases. Viral hemorrhagic fevers (VHFs) caused by these viruses are mostly characterized by an acute febrile syndrome with coagulation abnormalities and generalized hemorrhage that may lead to life-threatening organ dysfunction. Currently, the events underlying the viral pathogenicity associated with multiple organ dysfunction syndrome still underexplored. In this minireview, we address the current knowledge of the mechanisms underlying VHFs pathogenesis and discuss the available development of preventive and therapeutic options to treat these infections. Furthermore, we discuss the potential of HFVs to cause worldwide emergencies along with factors that favor their spread beyond their original niches.
RESUMO
We detected arenavirus RNA in 1.6% of 1,047 bats in Brazil that were sampled during 2007-2011. We identified Tacaribe virus in 2 Artibeus sp. bats and a new arenavirus species in Carollia perspicillata bats that we named Tietê mammarenavirus. Our results suggest that bats are an underrecognized arenavirus reservoir.
Assuntos
Arenavirus , Quirópteros , Animais , Arenavirus/genética , Brasil/epidemiologiaRESUMO
BACKGROUND: The spread of ticks has also led to the emergence of regional, previously unknown tick-borne diseases (TBDs) that pose an immediate threat to public health systems worldwide. People who spend time or work outdoors are at risk without closer awareness of regional exposures. That is especially true for tourists, who very easily come into contact with ticks and get bitten while hiking and climbing. A regional lack of surveillance, lack of awareness, lack of scientific background, and misdiagnosis makes it hard to assess the actual threat properly. METHODS: Therefore, this bibliometric study aims to assess the global research on ticks and some TBDs. Geographical and temporal patterns are elaborated under epidemiological and socioeconomic aspects. That will provide a factual basis for targeted action at the scientific, societal, and policy levels against the growing threat associated with ticks. RESULTS: The USA and Brazil can be identified as the key players in tick research, followed by Russia and some Central European countries. The socioeconomic analysis points to epidemiologically relevant regions, as also shown by comparison with the TBD analysis. A correlation between countries' gross domestic product and publication performance was found. Lack of scientific resources limits the necessary research and surveillance programs. CONCLUSIONS: Many regions that are popular travel destinations are threatened by new tick species and thus new health risks. Therefore, outdoor activities in many locations may pose an unknown hazard that requires regionally differentiated scientific investigation and better, globally networked research strategies.
Assuntos
Doenças Transmitidas por Carrapatos , Carrapatos , Animais , Humanos , Doenças Transmitidas por Carrapatos/epidemiologia , Doenças Transmitidas por Carrapatos/prevenção & controle , Europa (Continente) , Brasil , Federação RussaRESUMO
Resumen Desde la identificación del virus Junin en la década del 50, se realizaron numerosos estudios en roedores silvestres dentro del área endémica de la Fiebre Hemorrágica Argentina (FHA) que per mitieron registrar, además, actividad del virus de la coriomeningitis linfocitaria (LCMV) y del virus Latino (LATV). La ausencia de casos confirmados de FHA desde la década del 90 en el departamento Río Cuarto, provincia de Córdoba, promovió la vigilancia ecoepidemiológica y de infección del Calomys musculinus (reservorio del virus Junin) y la búsqueda de reservorios e infección de los otros mammarenavirus. Durante dos años de muestreo estacional, con un sistema de captura, marcación y liberación capturamos 857 roedores, que correspondieron 57.3% a los reservorios: C. musculinus (especie más abundante), C. venustus y Mus musculus. Detectamos anticuerpos y caracterizamos molecularmente los tres agentes virales. Observamos una prevalencia de infección de 3.5% (9/254) para virus Junin, 100% (3/3) para LCMV y 24.1% (21/87) para LATV. En conclusión, demostra mos circulación de virus Junin en su roedor reservorio, en una región considerada histórica para FHA con riesgo potencial para la población y cocirculación espacio-temporal de los tres mammarenavirus en la región central de Argentina.
Abstract Since the identification of Junin virus in the 1950s, many studies were carried out in wild rodents within the endemic area of the Argentine Hemorrhagic Fe ver (AHF) that recorded also the activity of the lymphocytic choriomeningitis virus (LCMV) and the Latino virus (LATV). The absence of confirmed cases of AHF since the 1990s in the department of Rio Cuarto, Córdoba province, promoted ecoepidemiological surveillance of infection of Calomys musculinus (Junin virus reservoir) and the search of reservoirs of the other mammarenaviruses. During two years of seasonal sampling, with a capture, mark and release system, 857 rodents were captured, corresponding 57.3% to the rodent reservoirs: C. musculinus, C. venustus and Mus musculus, being the first the most abundant species. Antibodies were detected and the three viral agents were molecularly characterized, showing a prevalence of infection of 3.5% (9/254) for Junin virus, 100% (3/3) for LCMV and 24.1% (21/87) for LATV. In conclusion, we demonstrated Junin virus circulation in its rodent reservoir in a region considered historic for AHF with potential risk for the population and the spatio-temporal co-circulation of the three mammarenaviruses in the central region of Argentina.
RESUMO
Junín virus (JUNV) belongs to the Arenaviridae family and is the causative agent of Argentine hemorrhagic fever (AHF), a severe human disease endemic to agricultural areas in Argentina. At this moment, there are no effective antiviral therapeutics to battle pathogenic arenaviruses. Cumulative reports from recent years have widely provided information on cellular factors playing key roles during JUNV infection. In this review, we summarize research on host molecular determinants that intervene in the different stages of the viral life cycle: viral entry, replication, assembly and budding. Alongside, we describe JUNV tight interplay with the innate immune system. We also review the development of different reverse genetics systems and their use as tools to study JUNV biology and its close teamwork with the host. Elucidating relevant interactions of the virus with the host cell machinery is highly necessary to better understand the mechanistic basis beyond virus multiplication, disease pathogenesis and viral subversion of the immune response. Altogether, this knowledge becomes essential for identifying potential targets for the rational design of novel antiviral treatments to combat JUNV as well as other pathogenic arenaviruses.
Assuntos
Arenaviridae , Arenavirus , Febre Hemorrágica Americana , Vírus Junin , Antivirais , Arenaviridae/genética , Humanos , Vírus Junin/fisiologia , Replicação ViralRESUMO
Since the identification of Junin virus in the 1950s, many studies were carried out in wild rodents within the endemic area of the Argentine Hemorrhagic Fever (AHF) that recorded also the activity of the lymphocytic choriomeningitis virus (LCMV) and the Latino virus (LATV). The absence of confirmed cases of AHF since the 1990s in the department of Rio Cuarto, Córdoba province, promoted ecoepidemiological surveillance of infection of Calomys musculinus (Junin virus reservoir) and the search of reservoirs of the other mammarenaviruses. During two years of seasonal sampling, with a capture, mark and release system, 857 rodents were captured, corresponding 57.3% to the rodent reservoirs: C. musculinus, C. venustus and Mus musculus, being the first the most abundant species. Antibodies were detected and the three viral agents were molecularly characterized, showing a prevalence of infection of 3.5% (9/254) for Junin virus, 100% (3/3) for LCMV and 24.1% (21/87) for LATV. In conclusion, we demonstrated Junin virus circulation in its rodent reservoir in a region considered historic for AHF with potential risk for the population and the spatio-temporal co-circulation of the three mammarenaviruses in the central region of Argentina.
Desde la identificación del virus Junin en la década del 50, se realizaron numerosos estudios en roedores silvestres dentro del área endémica de la Fiebre Hemorrágica Argentina (FHA) que permitieron registrar, además, actividad del virus de la coriomeningitis linfocitaria (LCMV) y del virus Latino (LATV). La ausencia de casos confirmados de FHA desde la década del 90 en el departamento Río Cuarto, provincia de Córdoba, promovió la vigilancia ecoepidemiológica y de infección del Calomys musculinus (reservorio del virus Junin) y la búsqueda de reservorios e infección de los otros mammarenavirus. Durante dos años de muestreo estacional, con un sistema de captura, marcación y liberación capturamos 857 roedores, que correspondieron 57.3% a los reservorios: C. musculinus (especie más abundante), C. venustus y Mus musculus. Detectamos anticuerpos y caracterizamos molecularmente los tres agentes virales. Observamos una prevalencia de infección de 3.5% (9/254) para virus Junin, 100% (3/3) para LCMV y 24.1% (21/87) para LATV. En conclusión, demostramos circulación de virus Junin en su roedor reservorio, en una región considerada histórica para FHA con riesgo potencial para la población y cocirculación espacio-temporal de los tres mammarenavirus en la región central de Argentina.
Assuntos
Arenaviridae , Arenavirus do Novo Mundo , Febre Hemorrágica Americana , Vírus Junin , Animais , Reservatórios de Doenças , Febre Hemorrágica Americana/epidemiologia , Humanos , Camundongos , RoedoresRESUMO
BACKGROUND: Only two naturally occurring human Sabiá virus (SABV) infections have been reported, and those occurred over 20 years ago. METHODS: We diagnosed two new cases of SABV infection using metagenomics in patients thought to have severe yellow fever and described new features of histopathological findings. RESULTS: We characterized clinical manifestations, histopathology and analyzed possible nosocomial transmission. Patients presented with hepatitis, bleeding, neurological alterations and died. We traced twenty-nine hospital contacts and evaluated them clinically and by RT-PCR and neutralizing antibodies. Autopsies uncovered unique features on electron microscopy, such as hepatocyte "pinewood knot" lesions. Although previous reports with similar New-World arenavirus had nosocomial transmission, our data did not find any case in contact tracing. CONCLUSIONS: Although an apparent by rare, Brazilian mammarenavirus infection is an etiology for acute hemorrhagic fever syndrome. The two fatal cases had peculiar histopathological findings not previously described. The virological diagnosis was possible only by contemporary techniques such as metagenomic assays. We found no subsequent infections when we used serological and molecular tests to evaluate close contacts.
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Arenavirus do Novo Mundo , Infecção Hospitalar , Febre Amarela , Anticorpos Neutralizantes , Brasil/epidemiologia , HumanosRESUMO
In the Americas, infectious viral diseases caused by viruses of the genus Mammarenavirus have been reported since the 1960s. Such diseases have commonly been associated with land use changes, which favor abundance of generalist rodent species. In the Americas-where the rates of land use change are among the highest worldwide-at least 1326 of all 2277 known rodent species have been reported. We conducted a literature review of studies between 1960 and 2020, to establish the current and historical knowledge about genotypes of mammarenaviruses and their rodent reservoirs in the Americas. Our overall goal was to show the importance of focusing research efforts on the American continent, since the conditions exist for future viral hemorrhagic fever (VHF) outbreaks caused by rodent-borne viruses, in turn, carried by widely distributed rodents. We found 47 species identified down to the species level, and one species identified only down to the genus level (Oryzomys sp.), reported in the Americas as reservoirs of mammarenaviruses, most these are ecological generalists. These species associate with 29 genotypes of Mammarenavirus, seven of which have been linked to VHFs in humans. We also highlight the need to monitor these species, in order to prevent viral disease outbreaks in the region.
Assuntos
Arenaviridae , Roedores , América , Animais , Arenaviridae/classificação , Arenaviridae/genética , Reservatórios de Doenças/virologia , Febres Hemorrágicas Virais/virologia , Roedores/virologiaRESUMO
Hemorrhagic fever viruses (HFVs) pose a threat to global public health owing to the emergence and re-emergence of highly fatal diseases. Viral hemorrhagic fevers (VHFs) caused by these viruses are mostly characterized by an acute febrile syndrome with coagulation abnormalities and generalized hemorrhage that may lead to life-threatening organ dysfunction. Currently, the events underlying the viral pathogenicity associated with multiple organ dysfunction syndrome still underexplored. In this minireview, we address the current knowledge of the mechanisms underlying VHFs pathogenesis and discuss the available development of preventive and therapeutic options to treat these infections. Furthermore, we discuss the potential of HFVs to cause worldwide emergencies along with factors that favor their spread beyond their original niches.
RESUMO
Chapare hemorrhagic fever is an emerging zoonotic disease caused by a Mammarenavirus, of the Arenaviridae family, called Chapare virus. Its name refers to the region in which it first appeared. This virus is transmitted through direct contact with the excreta of wild rodents that interact with humans by invading homes close to a rural area and when humans enter the jungle for various reasons such as agriculture and tourism, among others. This virus has been classified by the World Health Organization as biosafety level IV, where pathogens with the highest risk for humans are included and for which there are no vaccines available. It produces a febrile and hemorrhagic picture that leads to death two weeks after the onset of symptoms. There is no vaccine or standardized treatment to treat this disease. The bio ecological aspects of the reservoir are not known, nor are the factors that could be related to the emergency in the area. An investigation should be carried out focused mainly on knowing the circulation of the Chapare virus in the Bolivian tropics, knowing the bioecological characteristics of the reservoir to produce and contribute with reliable information for the design of future surveillance and control strategies with community participation, as well as to strengthen laboratory diagnostic capacities in health establishments in the municipality of Villa Tunari.
La fiebre hemorrágica Chapare es una enfermedad zoonótica emergente causada por un Mammarenavirus de la familia Arenaviridae, llamado virus Chapare; su nombre se debe a la región en la cual apareció por primera vez. Este virus es transmitido por medio del contacto directo con las excretas de los roedores silvestres que interactúan con el ser humano, al invadir las viviendas que se encuentran cercanas al área silvestre y cuando el hombre incursiona a la selva por diversas razones, como las actividades de agricultura o turismo, entre otras. Este virus ha sido catalogado por la Organización Mundial de la Salud como nivel de bioseguridad IV, en el cual se ubican los patógenos de mayor riesgo para el ser humano y para los cuales no existen vacunas disponibles. Produce un cuadro febril y hemorrágico que lleva al fallecimiento a las dos semanas de haber iniciado los síntomas. No existe vacuna ni tratamiento estandarizado para tratar esta enfermedad, no se conocen los aspectos bioecológicos del reservorio y tampoco los factores que podrían estar relacionados con la emergencia en la zona. Se deberá realizar una investigación enfocada principalmente en conocer la circulación del virus Chapare en la región del trópico boliviano, conocer las características bioecológicas del reservorio con el propósito de producir y aportar con información fehaciente para el diseño de futuras estrategias de vigilancia y control con participación comunitaria, así como fortalecer las capacidades de diagnóstico de laboratorio en los establecimientos de salud del municipio de Villa Tunari.
Assuntos
Arenavirus do Novo Mundo , Zoonoses , Arenavirus , HemorragiaRESUMO
Venezuelan Haemorrhagic Fever is an endemic zoonosis exhibiting a high lethality. Discovered decades ago, it is still causing seasonal hemorrhagic fever outbreaks. With the ongoing migration crisis, transmission and spreading to other countries in Latin America remains a latent threat that should be monitored, particularly in light of recent cases.
RESUMO
Neutrophils are first-line responders to infections and are recruited to target tissues through the action of chemoattractant molecules, such as chemokines. Neutrophils are crucial for the control of bacterial and fungal infections, but their role in the context of viral infections has been understudied. Flaviviruses are important human viral pathogens transmitted by arthropods. Infection with a flavivirus may result in a variety of complex disease manifestations, including hemorrhagic fever, encephalitis or congenital malformations. Our understanding of flaviviral diseases is incomplete, and so is the role of neutrophils in such diseases. Here we present a comprehensive overview on the participation of neutrophils in severe disease forms evolving from flavivirus infection, focusing on the role of chemokines and their receptors as main drivers of neutrophil function. Neutrophil activation during viral infection was shown to interfere in viral replication through effector functions, but the resulting inflammation is significant and may be detrimental to the host. For congenital infections in humans, neutrophil recruitment mediated by CXCL8 would be catastrophic. Evidence suggests that control of neutrophil recruitment to flavivirus-infected tissues may reduce immunopathology in experimental models and patients, with minimal loss to viral clearance. Further investigation on the roles of neutrophils in flaviviral infections may reveal unappreciated functions of this leukocyte population while increasing our understanding of flaviviral disease pathogenesis in its multiple forms.