RESUMO
BACKGROUND: In June 2019, the Bolivian Ministry of Health reported a cluster of cases of hemorrhagic fever that started in the municipality of Caranavi and expanded to La Paz. The cause of these cases was unknown. METHODS: We obtained samples for next-generation sequencing and virus isolation. Human and rodent specimens were tested by means of virus-specific real-time quantitative reverse-transcriptase-polymerase-chain-reaction assays, next-generation sequencing, and virus isolation. RESULTS: Nine cases of hemorrhagic fever were identified; four of the patients with this illness died. The etiologic agent was identified as Mammarenavirus Chapare mammarenavirus, or Chapare virus (CHAPV), which causes Chapare hemorrhagic fever (CHHF). Probable nosocomial transmission among health care workers was identified. Some patients with CHHF had neurologic manifestations, and those who survived had a prolonged recovery period. CHAPV RNA was detected in a variety of human body fluids (including blood; urine; nasopharyngeal, oropharyngeal, and bronchoalveolar-lavage fluid; conjunctiva; and semen) and in specimens obtained from captured small-eared pygmy rice rats (Oligoryzomys microtis). In survivors of CHHF, viral RNA was detected up to 170 days after symptom onset; CHAPV was isolated from a semen sample obtained 86 days after symptom onset. CONCLUSIONS: M. Chapare mammarenavirus was identified as the etiologic agent of CHHF. Both spillover from a zoonotic reservoir and possible person-to-person transmission were identified. This virus was detected in a rodent species, O. microtis. (Funded by the Bolivian Ministry of Health and others.).
Assuntos
Arenavirus do Novo Mundo , Febre Hemorrágica Americana , RNA Viral , Roedores , Animais , Arenavirus do Novo Mundo/genética , Arenavirus do Novo Mundo/isolamento & purificação , Bolívia/epidemiologia , Infecção Hospitalar/transmissão , Infecção Hospitalar/virologia , Transmissão de Doença Infecciosa , Febre Hemorrágica Americana/complicações , Febre Hemorrágica Americana/genética , Febre Hemorrágica Americana/transmissão , Febre Hemorrágica Americana/virologia , Febres Hemorrágicas Virais/genética , Febres Hemorrágicas Virais/transmissão , Febres Hemorrágicas Virais/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Reação em Cadeia da Polimerase , RNA Viral/genética , RNA Viral/isolamento & purificação , Ratos/virologia , Roedores/virologia , Zoonoses Virais/transmissão , Zoonoses Virais/virologiaRESUMO
We investigated hantaviruses in rodents in the southern Amazon Basin of Peru and identified an Andes virus variant from Neacomys spinosus mice. This finding extends the known range of this virus in South America and the range of recognized hantaviruses in Peru. Further studies of the epizoology of hantaviruses in this region are warranted.
Assuntos
Infecções por Hantavirus/veterinária , Orthohantavírus/genética , RNA Viral/classificação , Doenças dos Roedores , Sigmodontinae/virologia , Animais , Reservatórios de Doenças , Feminino , Orthohantavírus/classificação , Orthohantavírus/isolamento & purificação , Infecções por Hantavirus/epidemiologia , Infecções por Hantavirus/virologia , Masculino , Peru/epidemiologia , Filogenia , RNA Viral/genéticaRESUMO
Hantavirus pulmonary syndrome (HPS) is a severe disease characterized by a rapid onset of pulmonary edema followed by respiratory failure and cardiogenic shock. The HPS associated viruses are members of the genus Hantavirus, family Bunyaviridae. Hantaviruses have a worldwide distribution and are broadly split into the New World hantaviruses, which includes those causing HPS, and the Old World hantaviruses [including the prototype Hantaan virus (HTNV)], which are associated with a different disease, hemorrhagic fever with renal syndrome (HFRS). Sin Nombre virus (SNV) and Andes virus (ANDV) are the most common causes of HPS in North and South America, respectively. Case fatality of HPS is approximately 40%. Pathogenic New World hantaviruses infect the lung microvascular endothelium without causing any virus induced cytopathic effect. However, virus infection results in microvascular leakage, which is the hallmark of HPS. This article briefly reviews the knowledge on HPS-associated hantaviruses accumulated since their discovery, less than 20 years ago.
Assuntos
Genoma Viral , Vírus Hantaan/fisiologia , Síndrome Pulmonar por Hantavirus/virologia , Febre Hemorrágica com Síndrome Renal/virologia , Pulmão/virologia , Orthohantavírus/fisiologia , Insuficiência Respiratória/virologia , Choque Cardiogênico/virologia , Vírus Sin Nombre/fisiologia , Animais , Antivirais/administração & dosagem , Cricetinae , Europa (Continente) , Orthohantavírus/patogenicidade , Síndrome Pulmonar por Hantavirus/complicações , Síndrome Pulmonar por Hantavirus/tratamento farmacológico , Síndrome Pulmonar por Hantavirus/epidemiologia , Síndrome Pulmonar por Hantavirus/patologia , Febre Hemorrágica com Síndrome Renal/tratamento farmacológico , Febre Hemorrágica com Síndrome Renal/epidemiologia , Febre Hemorrágica com Síndrome Renal/patologia , Humanos , Pulmão/patologia , América do Norte , Filogeografia , Insuficiência Respiratória/tratamento farmacológico , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/patologia , Ribavirina/administração & dosagem , Choque Cardiogênico/tratamento farmacológico , Choque Cardiogênico/epidemiologia , Choque Cardiogênico/etiologia , Choque Cardiogênico/patologia , Vírus Sin Nombre/patogenicidade , América do SulRESUMO
Candid1, a live-attenuated Junin virus vaccine strain, was developed during the early 1980s to control Argentine hemorrhagic fever, a severe and frequently fatal human disease. Six amino acid substitutions were found to be unique to this vaccine strain, and their role in virulence attenuation in mice was analyzed using a series of recombinant viruses. Our results indicate that Candid1 is attenuated in mice through a single amino acid substitution in the transmembrane domain of the G2 glycoprotein. This work provides insight into the molecular mechanisms of attenuation of the only arenavirus vaccine currently available.
Assuntos
Vírus Junin/imunologia , Vírus Junin/patogenicidade , Mutação de Sentido Incorreto , Proteínas do Envelope Viral/genética , Vacinas Virais/genética , Fatores de Virulência/genética , Substituição de Aminoácidos/genética , Animais , Infecções por Arenaviridae/patologia , Infecções por Arenaviridae/virologia , Análise Mutacional de DNA , Modelos Animais de Doenças , Camundongos , Dados de Sequência Molecular , Mutação Puntual , Doenças dos Roedores/patologia , Doenças dos Roedores/virologia , Análise de Sequência de DNA , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologia , Proteínas do Envelope Viral/metabolismo , Vacinas Virais/imunologia , Fatores de Virulência/metabolismoRESUMO
Machupo virus and Chapare virus are members of the Tacaribe serocomplex (virus family Arenaviridae) and etiological agents of hemorrhagic fever in humans in Bolivia. The nucleotide sequences of the complete Z genes, a large fragment of the RNA-dependent RNA polymerase genes, the complete glycoprotein precursor genes, and the complete nucleocapsid protein genes of 8 strains of Machupo virus were determined to increase our knowledge of the genetic diversity among the Bolivian arenaviruses. The results of analyses of the predicted amino acid sequences of the glycoproteins of the Machupo virus strains and Chapare virus strain 200001071 indicated that immune plasma from hemorrhagic fever cases caused by Machupo virus may prove beneficial in the treatment of Bolivian hemorrhagic fever but not hemorrhagic fever caused by Chapare virus.
Assuntos
Arenavirus do Novo Mundo/genética , Variação Genética , RNA Viral/genética , Sequência de Aminoácidos , Animais , Infecções por Arenaviridae/virologia , Arenavirus do Novo Mundo/classificação , Bolívia , Chlorocebus aethiops , Evolução Molecular , Glicoproteínas/genética , Febre Hemorrágica Americana/virologia , Humanos , Proteínas do Nucleocapsídeo/genética , Filogenia , RNA Polimerase Dependente de RNA/genética , Alinhamento de Sequência , Análise de Sequência de RNA , Especificidade da Espécie , Células Vero , Proteínas do Envelope Viral/genéticaRESUMO
A small focus of hemorrhagic fever (HF) cases occurred near Cochabamba, Bolivia, in December 2003 and January 2004. Specimens were available from only one fatal case, which had a clinical course that included fever, headache, arthralgia, myalgia, and vomiting with subsequent deterioration and multiple hemorrhagic signs. A non-cytopathic virus was isolated from two of the patient serum samples, and identified as an arenavirus by IFA staining with a rabbit polyvalent antiserum raised against South American arenaviruses known to be associated with HF (Guanarito, Machupo, and Sabiá). RT-PCR analysis and subsequent analysis of the complete virus S and L RNA segment sequences identified the virus as a member of the New World Clade B arenaviruses, which includes all the pathogenic South American arenaviruses. The virus was shown to be most closely related to Sabiá virus, but with 26% and 30% nucleotide difference in the S and L segments, and 26%, 28%, 15% and 22% amino acid differences for the L, Z, N, and GP proteins, respectively, indicating the virus represents a newly discovered arenavirus, for which we propose the name Chapare virus. In conclusion, two different arenaviruses, Machupo and Chapare, can be associated with severe HF cases in Bolivia.
Assuntos
Arenavirus do Novo Mundo/isolamento & purificação , Febre Hemorrágica Americana/virologia , Adulto , Arenavirus do Novo Mundo/classificação , Arenavirus do Novo Mundo/genética , Bolívia , Análise por Conglomerados , Diagnóstico Diferencial , Evolução Fatal , Genoma Viral , Febre Hemorrágica Americana/diagnóstico , Humanos , Masculino , Filogenia , RNA Viral/genética , Análise de Sequência , Homologia de Sequência de Aminoácidos , Dengue Grave/diagnóstico , Proteínas Virais , Febre Amarela/diagnósticoRESUMO
In August 2002, two cases of hantavirus pulmonary syndrome (HPS) were confirmed in Mineros and Concepcion, within the Santa Cruz Department of Bolivia. Extensive alteration of the native ecosystem, from dense forest to pasture or sugarcane, had occurred in both regions. An ecologic assessment of reservoir species associated with the human disease identified a single hantavirus antibody-positive Oligoryzomys microtis from Mineros and three hantavirus antibody-positive Calomys callosus from Concepcion. In Mineros, the virus from the O. microtis was 90% similar to sequences published for Rio Mamore virus. Viral nucleotide sequences from two C. callosus were 87-88% similar to the sequence of Laguna Negra virus. The viral sequence from the C. callosus was 99% identical to viral sequences obtained from the HPS patient in this area, implicating C. callosus as the host and Laguna Negra virus as the agent responsible for the HPS case near Concepcion.
Assuntos
Síndrome Pulmonar por Hantavirus/epidemiologia , Síndrome Pulmonar por Hantavirus/transmissão , Orthohantavírus/genética , Roedores/virologia , Animais , Bolívia/epidemiologia , Reservatórios de Doenças , Genótipo , Orthohantavírus/classificação , Orthohantavírus/isolamento & purificação , Síndrome Pulmonar por Hantavirus/sangue , Humanos , Dados de Sequência Molecular , Filogenia , RNA Viral/análise , Ratos , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
An outbreak of hantavirus pulmonary syndrome occurred in the province of Los Santos, Panama, in late 1999 and early 2000. Eleven cases were identified; 9 were confirmed by serology. Three cases were fatal; however, no confirmed case-patient died. Case-neighborhood serologic surveys resulted in an overall hantavirus antibody prevalence of 13% among household and neighborhood members from the outbreak foci. Epidemiologic investigations did not suggest person-to-person transmission of hantavirus infection. By use of Sin Nombre virus antigen, hantavirus antibodies were detected in Oligoryzomys fulvescens and Zygodontomys brevicauda cherriei. This outbreak resulted in the first documented cases of human hantavirus infections in Central America.