Bunyavirales

Bunyaviridae Bunyaviridae A family of viruses, mainly arboviruses, consisting of a single strand of RNA. Virions are enveloped particles 90-120 nm diameter. The complete family contains over 300 members arranged in five genera: orthobunyavirus; hantavirus; nairovirus; phlebovirus; and tospovirus. Bunyavirales é uma família de vírus de RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure classificada em 5 géneros: Orthobunyavirus Orthobunyavirus A genus of the family bunyaviridae containing over 150 viruses, most of which are transmitted by mosquitoes or flies. They are arranged in groups defined by serological criteria, each now named for the original reference species (previously called serogroups). Many species have multiple serotypes or strains. Bunyavirales (vírus La Crosse), Hantavirus Hantavirus A genus of the family bunyaviridae causing hantavirus infections, first identified during the korean war. Infection is found primarily in rodents and humans. Transmission does not appear to involve arthropods. Hantaan virus is the type species. Bunyavirales, Nairovirus Nairovirus A genus of the family bunyaviridae named after nairobi sheep disease, an acute, hemorrhagic, tick-borne, gastroenteritis affecting sheep and goats. The type species is dugbe virus. Some viruses in this genus are capable of causing severe and fatal disease in humans. Bunyavirales (vírus da febre hemorrágica da Crimeia-Congo), Phlebovirus Phlebovirus A genus of the family bunyaviridae comprising many viruses, most of which are transmitted by phlebotomus flies and cause phlebotomus fever. The type species is rift valley fever virus. Bunyavirales (vírus da febre do Vale do Rift) e Tospovirus Tospovirus A genus of plant viruses in the family bunyaviridae. Tomato spotted wilt virus is the type species. Transmission occurs by at least nine species of thrips. Bunyavirales. As características comuns desta família de vírus incluem uma estrutura esférica com invólucro contendo um genoma de RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure de cadeia simples e sentido negativo, com 3 segmentos. As infeções são geralmente transmitidas por artrópodes ou por roedores. Existem várias manifestações clínicas, mas, em geral, apresentam-se como febres hemorrágicas e/ou encefalites. Os exames de diagnóstico incluem a serologia e o RT-PCR RT-PCR A variation of the pcr technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard pcr protocols. Polymerase Chain Reaction (PCR). O tratamento é de suporte.

Last updated: Feb 23, 2025

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Classificação

Classificação do fluxograma de vírus de RNA

Identificação do vírus RNA:
Os vírus podem ser classificados de várias maneiras. A maioria dos vírus, no entanto, terá um genoma formado por DNA ou RNA. Os vírus de genoma de RNA podem ser ainda caracterizados com base na presença de RNA de fita simples ou dupla. Os vírus “envelopados” são cobertos por uma fina camada de membrana celular (geralmente retirada da célula hospedeira). Se a pelagem estiver ausente, os vírus são chamados de vírus “nus”. Vírus com genomas de fita simples são chamados de vírus de “sentido positivo” se o genoma for usado diretamente como RNA mensageiro (mRNA), que é traduzido em proteínas. Os vírus de “sentido negativo” de fita simples usam RNA polimerase dependente de RNA, uma enzima viral, para transcrever seu genoma em RNA mensageiro.

Imagem de Lecturio. Licença: CC BY-NC-SA 4.0

Características

Características básicas

  • Taxonomia:
    • Ordem: Bunyavirales Bunyavirales Bunyaviridae is a family of RNA viruses that is classified into 5 genera: Orthobunyavirus (La Crosse virus), Hantavirus, Nairovirus (Crimean-Congo hemorrhagic fever virus), Phlebovirus (Rift Valley fever virus), and Tospovirus. The common characteristics of the virus family include an enveloped spherical structure containing a single-stranded, negative-sense RNA genome, which is triple-segmented. Bunyavirales
    • Família: Bunyaviridae Bunyaviridae A family of viruses, mainly arboviruses, consisting of a single strand of RNA. Virions are enveloped particles 90-120 nm diameter. The complete family contains over 300 members arranged in five genera: orthobunyavirus; hantavirus; nairovirus; phlebovirus; and tospovirus. Bunyavirales
    • 5 géneros:
      • Hantavirus Hantavirus A genus of the family bunyaviridae causing hantavirus infections, first identified during the korean war. Infection is found primarily in rodents and humans. Transmission does not appear to involve arthropods. Hantaan virus is the type species. Bunyavirales/Orthohantavirus (inclui o vírus Sin Nombre)
      • Orthobunyavirus Orthobunyavirus A genus of the family bunyaviridae containing over 150 viruses, most of which are transmitted by mosquitoes or flies. They are arranged in groups defined by serological criteria, each now named for the original reference species (previously called serogroups). Many species have multiple serotypes or strains. Bunyavirales (inclui o vírus La Crosse)
      • Phlebovirus Phlebovirus A genus of the family bunyaviridae comprising many viruses, most of which are transmitted by phlebotomus flies and cause phlebotomus fever. The type species is rift valley fever virus. Bunyavirales (inclui o vírus da febre do Vale do Rift (RVF), vírus da febre da mosca da areia / phlebotomus)
      • Nairovirus Nairovirus A genus of the family bunyaviridae named after nairobi sheep disease, an acute, hemorrhagic, tick-borne, gastroenteritis affecting sheep and goats. The type species is dugbe virus. Some viruses in this genus are capable of causing severe and fatal disease in humans. Bunyavirales (inclui a febre hemorrágica da Crimeia-Congo)
      • Tospovirus Tospovirus A genus of plant viruses in the family bunyaviridae. Tomato spotted wilt virus is the type species. Transmission occurs by at least nine species of thrips. Bunyavirales (infeta apenas plantas)
  • Bunyavirus:
    • Com invólucro: invólucro com 2 glicoproteínas
    • Esférico, 80-120nm de diâmetro
    • Genoma:
      • Vírus de RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure de cadeia simples de sentido negativo
      • Com 3 segmentos
      • Cápside helicoidal
      • Contém uma RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure polimerase dependente de RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure
    • São vírus transmitidos sobretudo por artrópodes ou por roedores:
      • Hantavirus Hantavirus A genus of the family bunyaviridae causing hantavirus infections, first identified during the korean war. Infection is found primarily in rodents and humans. Transmission does not appear to involve arthropods. Hantaan virus is the type species. Bunyavirales (roedores)
      • Orthobunyavirus Orthobunyavirus A genus of the family bunyaviridae containing over 150 viruses, most of which are transmitted by mosquitoes or flies. They are arranged in groups defined by serological criteria, each now named for the original reference species (previously called serogroups). Many species have multiple serotypes or strains. Bunyavirales (mosquitos)
      • Nairovirus Nairovirus A genus of the family bunyaviridae named after nairobi sheep disease, an acute, hemorrhagic, tick-borne, gastroenteritis affecting sheep and goats. The type species is dugbe virus. Some viruses in this genus are capable of causing severe and fatal disease in humans. Bunyavirales (carraças)
      • Phlebovirus Phlebovirus A genus of the family bunyaviridae comprising many viruses, most of which are transmitted by phlebotomus flies and cause phlebotomus fever. The type species is rift valley fever virus. Bunyavirales: vírus da febre da mosca da areia (flebotomíneos)
      • Phlebovirus Phlebovirus A genus of the family bunyaviridae comprising many viruses, most of which are transmitted by phlebotomus flies and cause phlebotomus fever. The type species is rift valley fever virus. Bunyavirales: vírus da RVF (mosquitos)
    • Doenças associadas:
      • Febres hemorrágicas (ou seja, Hantavirus Hantavirus A genus of the family bunyaviridae causing hantavirus infections, first identified during the korean war. Infection is found primarily in rodents and humans. Transmission does not appear to involve arthropods. Hantaan virus is the type species. Bunyavirales, febre hemorrágica da Crimeia-Congo)
      • Encefalite transmitida por mosquitos (ou seja, grupo de encefalites da Califórnia, que inclui o vírus La Crosse)

Related videos

Hantavirus

Etiologia e Epidemiologia

  • Género: Hantavirus Hantavirus A genus of the family bunyaviridae causing hantavirus infections, first identified during the korean war. Infection is found primarily in rodents and humans. Transmission does not appear to involve arthropods. Hantaan virus is the type species. Bunyavirales
  • > 20 espécies (cerca de 11 são conhecidas por causar doença em humanos), incluindo:
    • Vírus Sin Nombre:
      • Etiologia do surto de 1993 “Four Corners” no sudoeste dos EUA
      • Encontra-se entre as etiologias da síndrome pulmonar por hantavírus (HPS) /síndrome cardiopulmonar por hantavírus (HCPS), podendo causar uma doença respiratória grave e potencialmente fatal
    • Vírus Seoul, Dobrava e Puumala: entre os agentes etiológicos da febre hemorrágica com síndrome renal (HFRS)
  • Epidemiologia:
    • A China tem a maior incidência anual de doenças relacionadas com o hantavírus.
    • 864 casos reportados nos EUA em 2022 (encontrado mais MAIS Androgen Insensitivity Syndrome comummente nos estados do oeste e sudoeste)
    • A maioria das infeções nos EUA é esporádica.
Uma partícula de vírus Sin Nombre Hantavirus Bunyavirales

Imagem de uma partícula do vírus Sin Nombre a sair de uma célula Vero:
O vírus Sin Nombre causa a síndrome pulmonar por hantavírus na América do Norte.

Imagem: “A Sin Nombre virus particle shown budding from a Vero cell” de NIAID. Licença: CC BY 2.0

Fisiopatologia

  • Reservatório primário: roedores (ratos-veadeiros nos EUA)
  • Transmissão:
    • Aerossolização/inalação (exposição a fezes, saliva Saliva The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin. Salivary Glands: Anatomy ou urina de ratos infetados)
    • Mordedura do roedor
    • Contacto direto (pelo nariz ou boca) com materiais contaminados com excrementos, saliva Saliva The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin. Salivary Glands: Anatomy ou urina de roedores
    • Ingestão de excrementos, saliva Saliva The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin. Salivary Glands: Anatomy ou urina de roedores
  • Principais síndromes/mecanismos de doença:
    • HPS
      • Os antigénios virais penetram no endotélio, levando a uma resposta imunológica → ↑ permeabilidade capilar → edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema pulmonar
      • A mais MAIS Androgen Insensitivity Syndrome fatal das 2 síndromes por hantavírus
      • Causada principalmente por espécies de hantavírus nas Américas, e geralmente ocorre no outono nos EUA
    • HFRS
      • Azotemia Azotemia A biochemical abnormality referring to an elevation of blood urea nitrogen and creatinine. Azotemia can be produced by kidney diseases or other extrarenal disorders. When azotemia becomes associated with a constellation of clinical signs, it is termed uremia. Acute Kidney Injury secundária a lesão endotelial vascular (extravazamento capilar e perda de líquidos)
      • Lesão tubular e intersticial induzida pelas citocinas → nefrite tubulointersticial
      • A mais MAIS Androgen Insensitivity Syndrome comum das 2 síndromes de hantavírus
      • Causada principalmente por espécies de hantavírus na Ásia e na Europa
Transmissão do Hantavírus

Transmissão do hantavírus:
Os investigadores descobriram que o contacto com roedores e respetivos resíduos coloca os humanos em risco de exposição ao hantavírus. As chuvas maciças associadas ao El Niño de 1991–1992 aumentaram a produtividade das plantas.
A população de roedores cresceu devido à abundância de matéria vegetal. O aumento do contacto com os roedores e os seus resíduos coloca mais humanos em risco de exposição ao hantavírus.

Imagem: “Researchers found that contact with rodents and their waste puts humans at risk for exposure to hantavirus” de Zina Deretsky, National Science Foundation.  Licença: Domínio Público

Apresentação clínica

  • HPS/HCPS:
    • Período de incubação: 1-3 semanas
    • Fase prodrómica (até 5 dias):
      • Febre
      • Cefaleias
      • Dores musculares
      • Náuseas/vómitos/diarreia
    • Fase cardiopulmonar (2-7 dias):
      • Tosse
      • Dispneia: pode evoluir para hipóxia e insuficiência respiratória necessitando de ventilação mecânica
      • Hipotensão
      • Oligúria
      • Achados: taquipneia, taquicardia
    • Fase de convalescença:
      • Diurese significativa
      • Resolução dos sintomas
  • HFRS:
    • Varia consoante a espécie (ou seja, o vírus Hantaan na Ásia causa doença mais MAIS Androgen Insensitivity Syndrome grave)
    • As manifestações incluem:
      • Febre
      • Hipotensão (pode levar ao choque)
      • Hemorragia
      • LRA (↓ TFG, oligúria, proteinúria e hematúria)

Diagnóstico e Tratamento

  • Testes Testes Gonadal Hormones de confirmação:
    • Serologia (ou seja, ELISA ELISA An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. St. Louis Encephalitis Virus), na qual a infeção aguda é detetada como:
      • IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions anti-hantavírus específico (geralmente anti nucleocápside ou antigénio N)
      • Uma elevação de 4 vezes nos títulos de IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis anti-hantavírus
    • RT-PCR RT-PCR A variation of the pcr technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard pcr protocols. Polymerase Chain Reaction (PCR) no plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products, células sanguíneas ou tecidos
  • Análises laboratoriais adicionais:
    • Hemograma: leucocitose, trombocitopenia
    • Painel hepático: ↑ transaminases Transaminases A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. Autoimmune Hepatitis, ↓ albumina
    • HFRS: Alteração do rácio BUN/creatinina, proteinúria ou hematúria
    • PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR)
  • Radiografia de tórax:
    • HPS:
      • Edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema intersticial (na maioria dos doentes após 48 horas)
      • Opacidades perihilares sem cardiomegalia
    • HFRS:
      • Pode mostrar alterações na radiografia de tórax
      • Infiltrados intersticiais, derrame, atelectasia
  • Tratamento:
    • Medidas de suporte:
      • Suporte cardiorrespiratório
      • Balanço hídrico
      • Diálise conforme indicado
    • Prevenção: controlo de roedores, evitando o contacto com roedores e realizando uma limpeza adequada dos locais de nidificação.
    • Não existe vacinação disponível
  • Mortalidade:
    • HPS: até 35% no global
    • HFRS: 5%–10%
Tabela: Diagnóstico e tratamento
Síndrome pulmonar por hantavírus Febre hemorrágica por hantavírus
Incubação 1-3 semanas 1-3 semanas (até 6 semanas)
Diagnóstico
  • Serologia
  • RT-PCR RT-PCR A variation of the pcr technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard pcr protocols. Polymerase Chain Reaction (PCR)
  • Serologia
  • RT-PCR RT-PCR A variation of the pcr technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard pcr protocols. Polymerase Chain Reaction (PCR)
Manifestações clínicas Pródromo: sintomas gripais, início súbito de dispneia com edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema pulmonar de evolução rápida Febre, hipotensão/choque, LRA
AP radiografia de tórax síndrome pulmonar por hantavírus Bunyavírus

Radiografia de tórax anteroposterior que mostra um derrame pulmonar bilateral em fase intermédia devido à síndrome pulmonar por hantavírus (HPS):
A evolução radiológica da HPS inicia-se com alterações mínimas correspondentes a edema pulmonar intersticial, que progride para edema alveolar com atingimento bilateral grave. Os derrames pleurais são comuns e muitas vezes grandes o suficiente para serem evidentes radiograficamente.

Imagem: “This AP chest X-ray reveals the mid-staged bilateral pulmonary effusion due to hantavirus pulmonary syndrome, or HPS” do CDC/ D. Loren Ketai, M.D.  License: Public Domain

Vírus da Febre Hemorrágica da Crimeia-Congo

Etiologia e Epidemiologia

  • Género: Nairovirus Nairovirus A genus of the family bunyaviridae named after nairobi sheep disease, an acute, hemorrhagic, tick-borne, gastroenteritis affecting sheep and goats. The type species is dugbe virus. Some viruses in this genus are capable of causing severe and fatal disease in humans. Bunyavirales
  • Vírus da febre hemorrágica da Crimeia-Congo
  • Doença associada: febre hemorrágica da Crimeia-Congo
    • Caracterizada pela primeira vez na Crimeia em 1944 (febre da Crimeia)
    • Mais MAIS Androgen Insensitivity Syndrome tarde, foi reconhecida em 1956 como a causa da doença no Congo, resultando no nome atual da doença
  • Epidemiologia:
    • Áreas endémicas:
      • África (principalmente central)
      • Europa de Leste (particularmente na antiga União Soviética) e sul da Europa
      • Mediterrâneo
      • Médio Oriente
      • Noroeste da China
      • Ásia Central
      • Subcontinente indiano
    • Risco de exposição:
      • Criadores de animais
      • Trabalhadores da pecuária
      • Trabalhadores de matadouros
Schematic illustration of a nairovirus particle

Ilustração esquemática de uma partícula de nairovírus (RNA de cadeia única envelopado, contendo segmentos L, M, e S, rodeado por glicoproteínas externas)
RNP: ribonucleoproteína

Imagem por Lecturio.

Fisiopatologia

  • Vetor e reservatório: As carraças Ixodes (género: Hyalomma) conseguem transmitir o vírus à descendência.
  • Hospedeiros amplificadores: animais selvagens e domésticos, como bovinos, caprinos e ovinos.
  • Transmissão:
    • Mordeduras de carraças
    • Contacto direto com fluidos corporais de animais ou humanos infetados
    • Está documentada a transmissão através de equipamentos médicos esterilizados inadequadamente, picadas com agulhas e outros materiais médicos contaminados em hospitais.
    • Transmissão vertical (da mãe para o filho)
  • Mecanismo de doença:
    • O vírus replica-se no local da inoculação, no interior das células epiteliais, macrófagos e células dendríticas → virémia
    • As células endoteliais são o alvo do vírus, desencadeando a libertação de citocinas e de quimiocinas e levando a:
      • Aumento da permeabilidade vascular
      • Agregação plaquetária desregulada → é estimulada a cascata de coagulação (estado pró-trombótico)
      • Os fatores de coagulação tornam-se eventualmente deficitários → hemorragia

Apresentação clínica

  • Início súbito de sintomas gripais-like:
    • Cefaleias
    • Febre
    • Dores nas costas e artralgias
    • Dor abdominal
    • Náuseas/vómitos
    • Ruborização facial
    • Injeção conjuntival
    • Petéquias no palato
  • Os sintomas duram até 7 dias:
    • Na maioria das vezes segue-se de recuperação
    • Pode progredir para doença grave com hemorragia (equimose, epistaxis Epistaxis Bleeding from the nose. Granulomatosis with Polyangiitis, hemorragia gengival, hematúria, melenas, hemorragia menstrual intensa)
    • A resposta pró-inflamatória de citocinas (“tempestade de citocinas”) exagerada leva a hipotensão, choque e falência multiorgânica.
  • As taxas de mortalidade nos doentes hospitalizados variam de 9% a 50%.

Diagnóstico e tratamento

  • Exames complementares de diagnóstico:
    • O diagnóstico é baseado nos achados físicos e na história de exposição ao risco.
    • RT-PCR RT-PCR A variation of the pcr technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard pcr protocols. Polymerase Chain Reaction (PCR)
    • Serologia (deteção de imunoglobulinas específicas IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions e IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis através de ELISA ELISA An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. St. Louis Encephalitis Virus)
  • Exames laboratoriais adicionais:
    • Hemograma: trombocitopenia, leucopenia
    • Painel hepático: ↑ transaminases Transaminases A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. Autoimmune Hepatitis, hiperbilirrubinemia
    • ↑ PT/INR
    • Na coagulação intravascular disseminada: ↑ produtos de degradação da fibrina, ↓ fibrinogénio
  • Tratamento
    • De suporte:
      • Suporte cardiorrespiratório
      • Balanço hídrico
      • Substituição de hemoderivados
    • A ribavirina pode conferir algum benefício.
    • Não existe vacina disponível
  • Prevenção:
    • Evitar o contacto com sangue e fluidos corporais de animais infetados
    • Utilizar repelentes de insetos e roupas protetoras
    • Isolamento dos doentes
    • Utilizar EPI

Vírus da Febre do Vale do Rift

Etiologia e Epidemiologia

  • Género: Phlebovirus Phlebovirus A genus of the family bunyaviridae comprising many viruses, most of which are transmitted by phlebotomus flies and cause phlebotomus fever. The type species is rift valley fever virus. Bunyavirales
  • Vírus RVF
  • Doença associada: RVF (febre hemorrágica viral)
  • Epidemiologia:
    • Áreas endémicas:
      • Este de África
      • África subsariana
      • Madagáscar
    • Afeta geralmente o gado, mas os humanos são infetados de forma secundária.
Enveloped virions of Rift Valley fever virus (RVFV)

Os viriões envelopados do vírus da febre do Vale do Rifte caracterizam-se por um genoma RNA negativo ou ambisenso composto por 3 segmentos de cadeia simples (designados L, M, e S):
As 3 moléculas de RNA são encapsuladas por nucleoproteína (N), moldando a nucleocápside e interagindo com a polimerase viral (L). As glicoproteínas Gn e Gc são notadas externamente. As proteínas não-estruturais NSm e NSs são expressas durante a infeção.

Imagem por Lecturio.

Fisiopatologia

  • Vetor:
    • Mosquitos: As fêmeas conseguem transmitir o vírus aos seus ovos.
      • Mosquito Aedes (vetor primário)
      • Mosquito Culex
    • Animais infetados
  • Transmissão:
    • Picadas de mosquito
    • Contacto com sangue ou fluidos corporais de animais infetados
  • Fatores de risco do hospedeiro
    • Residir numa zona rural
    • Dormir ao ar AR Aortic regurgitation (AR) is a cardiac condition characterized by the backflow of blood from the aorta to the left ventricle during diastole. Aortic regurgitation is associated with an abnormal aortic valve and/or aortic root stemming from multiple causes, commonly rheumatic heart disease as well as congenital and degenerative valvular disorders. Aortic Regurgitation livre à noite
    • Pastores/agricultores
    • Veterinários
    • Talhantes/trabalhadores de matadouros

Apresentação clínica

  • A infeção por RVF pode causar doença ligeira ou grave em humanos.
    • Doença ligeira:
      • 90% dos casos
      • A maioria dos doentes tem um síndrome gripal ou é assintomático.
      • Recuperação em 2 dias a 1 semana
    • Doença grave:
      • 8%–10% dos casos
      • Doença ocular: retinite, lesões que afetam a mácula (50% terão cegueira permanente)
      • Febre hemorrágica (1% dos casos): hemorragia, insuficiência hepática, hematemeses (taxa de mortalidade de 50%)
      • Encefalite (1% dos casos): cefaleias, coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma, convulsões (pode levar a défices neurológicos permanentes)

Diagnóstico e tratamento

  • RT-PCR RT-PCR A variation of the pcr technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard pcr protocols. Polymerase Chain Reaction (PCR)
  • Isolamento do vírus em cultura de células
  • Serologia (anticorpos IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions contra o vírus RVF)
  • Tratamento
    • A maioria das infeções é autolimitada.
    • Tratamento de suporte
    • Não existem tratamentos aprovados pela FDA
  • Prevenção
    • Não existem vacinas para a prevenção.
    • Evitar o contacto com sangue e fluidos corporais de animais infetados.
    • Evicção de mosquitos:
      • Repelentes de insetos
      • Redes mosquiteiras
      • Roupa de proteção

Vírus La Crosse

Etiologia e Epidemiologia

  • Género: Orthobunyavirus Orthobunyavirus A genus of the family bunyaviridae containing over 150 viruses, most of which are transmitted by mosquitoes or flies. They are arranged in groups defined by serological criteria, each now named for the original reference species (previously called serogroups). Many species have multiple serotypes or strains. Bunyavirales
  • Vírus La Crosse: é o vírus mais MAIS Androgen Insensitivity Syndrome patogénico do serogrupo da encefalite da Califórnia
  • Doença associada: encefalite La Crosse (arbovirose transmitida por mosquitos)
  • Epidemiologia:
    • Vírus La Crosse: arbovírus mais MAIS Androgen Insensitivity Syndrome comum a causar infeções do SNC em crianças (América do Norte)
    • Aproximadamente 75% dos casos na população pediátrica
    • Nos E.U.A:
      • 30-120 casos de doenças neuroinvasivas reportados anualmente
      • A maioria dos casos é reportada no verão, com pico de incidência entre julho e setembro.
      • Áreas mais MAIS Androgen Insensitivity Syndrome afetadas: estados do alto centro-oeste, meio-atlântico e sudeste.
morfologia ultraestrutural exibida por numerosos vírus La Crosse Bunyavirales

Imagem que mostra a morfologia ultraestrutural de numerosas partículas do vírus La Crosse (LCV)

Imagem: Image showing the ultrastructural morphology exhibited by numerous La Crosse virus (LCV) particles” de Dr. Erskine Palmer, USCDCP.  Licença: Domínio Público

Fisiopatologia

  • Vetor: o mosquito do buraco da árvore oriental, Aedes triseriatus Aedes triseriatus Bunyavirales
  • Reservatório: A. triseriatus (o vírus é transmitido de um mosquito fêmea para os ovos)
  • Hospedeiros: Os ciclos de infeção ocorrem entre mosquitos e hospedeiros (humanos, esquilos e outros pequenos mamíferos).
  • Transmissão: picada de mosquito
  • Fisiopatologia
    • O vírus é transmitido subcutaneamente por um mosquito enquanto se alimenta.
    • A replicação viral inicia-se no músculo adjacente ao local de penetração, e pode seguir-se por virémia.
    • Ocorre a disseminação para o sistema reticuloendotelial (gânglios linfáticos, fígado, baço) e pode ocorrer neuroinvasão.

Apresentação clínica

  • Incubação: 3-7 dias
  • Muitos dos indivíduos infetados são assintomáticos ou apresentam uma doença ligeira semelhante à gripe:
    • Cefaleias
    • Náuseas, vómitos
    • Fadiga, letargia
  • Alguns dos indivíduos infetados podem desenvolver doença neuroinvasiva grave (na maioria das vezes crianças < 16 anos):
    • Encefalite
    • Convulsões
    • Meningite assética
    • Paralisia
    • Coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma
    • As mortes são raras.

Diagnóstico e tratamento

  • Suspeitar nos doentes que apresentam sintomas típicos numa área endémica.
  • Exames complementares de diagnóstico:
    • IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions e anticorpos neutralizantes do vírus no soro ou LCR através de um ELISA ELISA An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. St. Louis Encephalitis Virus
    • Elevação de 4 vezes nos títulos de anticorpos
    • Deteção de antigénios virais ou de sequências genómicas em tecidos, no sangue ou LCR
  • Exames adicionais:
    • A tomografia computadorizada cerebral é normal.
    • As alterações no EEG EEG Seizures são comuns.
  • Tratamento
    • Suporte
    • Geralmente autolimitada
    • Não existe nenhum fármaco antivírico eficaz
    • Não existe nenhuma vacina disponível
  • Prevenção
    • Evicção de mosquitos:
      • Repelente de insetos
      • Roupa de proteção
      • Evitar áreas infestadas de mosquitos

Comparação entre Espécies

Tabela: Comparação entre espécies
Organismo Hantavírus Vírus da febre hemorrágica da Crimeia-Congo Vírus da febre do Vale do Rift Vírus La Crosse
Características Vírus de RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure de cadeia simples e sentido negativo, com invólucro
Género Hantavirus Hantavirus A genus of the family bunyaviridae causing hantavirus infections, first identified during the korean war. Infection is found primarily in rodents and humans. Transmission does not appear to involve arthropods. Hantaan virus is the type species. Bunyavirales ou Ortohantavirus Nairovirus Nairovirus A genus of the family bunyaviridae named after nairobi sheep disease, an acute, hemorrhagic, tick-borne, gastroenteritis affecting sheep and goats. The type species is dugbe virus. Some viruses in this genus are capable of causing severe and fatal disease in humans. Bunyavirales Phlebovirus Phlebovirus A genus of the family bunyaviridae comprising many viruses, most of which are transmitted by phlebotomus flies and cause phlebotomus fever. The type species is rift valley fever virus. Bunyavirales Orthobunyvirus
Transmissão Inalação e contacto direto com a urina e fezes de roedores infetados Contacto com carraças infetadas (especialmente Hyalomma spp.)
  • Picadas de mosquito
  • Exposição a sangue e fluidos corporais de animais infetados
Picadas de mosquito
Apresentação clínica
  • Síndrome pulmonar por hantavírus
  • Febre hemorrágica com síndrome renal
Febre hemorrágica
  • Febre hemorrágica
  • Doença ocular
  • Encefalite
Encefalite
Diagnóstico
  • RT-PCR RT-PCR A variation of the pcr technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard pcr protocols. Polymerase Chain Reaction (PCR)
  • ELISA ELISA An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. St. Louis Encephalitis Virus (anticorpos)
  • RT-PCR RT-PCR A variation of the pcr technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard pcr protocols. Polymerase Chain Reaction (PCR)
  • ELISA ELISA An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. St. Louis Encephalitis Virus (anticorpos)
  • RT-PCR RT-PCR A variation of the pcr technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard pcr protocols. Polymerase Chain Reaction (PCR)
  • ELISA ELISA An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. St. Louis Encephalitis Virus (anticorpos)
  • ELISA ELISA An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. St. Louis Encephalitis Virus (anticorpos no soro ou LCR)
  • RT-PCR RT-PCR A variation of the pcr technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard pcr protocols. Polymerase Chain Reaction (PCR)
Tratamento Suporte
  • Suporte
  • Ribavirina
Suporte Suporte

Diagnóstico Diferencial

  • Vírus da encefalite de Saint Louis: membro do género Flavivirus Flavivirus A genus of flaviviridae containing several subgroups and many species. Most are arboviruses transmitted by mosquitoes or ticks. The type species is yellow fever virus. Tick-borne Encephalitis Virus e a causa da encefalite de Saint Louis. O vírus da encefalite de Saint Louis é um vírus pequeno de ssRNA de sentido positivo, com invólucro, transmitido por espécies de mosquitos Culex. A maioria das infeções é assintomática. Os indivíduos sintomáticos podem ter apresentações variadas com sintomas semelhantes aos da gripe, meningite assética, encefalite ou meningoencefalite. O diagnóstico é confirmado com serologia. Não existem fármacos antivíricos eficazes; por isso, o tratamento é de suporte. A prevenção visa o controlo local dos mosquitos e a proteção individual usando repelentes de insetos e roupas de proteção.
  • Febre amarela: doença causada pelo vírus da febre amarela, um vírus de RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure de sentido positivo de cadeia simples do género Flavivirus Flavivirus A genus of flaviviridae containing several subgroups and many species. Most are arboviruses transmitted by mosquitoes or ticks. The type species is yellow fever virus. Tick-borne Encephalitis Virus. Os humanos e os primatas servem como reservatórios, e a transmissão ocorre através da picada de um mosquito fêmea infetado. Os doentes apresentam febre e sintomas semelhantes aos da gripe na maioria dos casos. A doença grave pode causar disfunção multiorgânica resultando em icterícia, disfunção renal, hemorragia, choque e eventualmente morte. O diagnóstico pode ser confirmado com serologia e PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR). Não existem fármacos antivíricos disponíveis para tratar a febre amarela; por isso, o tratamento é de suporte. A prevenção inclui as medidas de prevenção dos mosquitos e a vacinação.
  • Vírus da encefalite transmitida por carraças ( TBEV TBEV Tick-borne encephalitis virus (TBEV) is a positive-sense, single-stranded RNA virus of the genus Flavivirus. Transmission occurs primarily via Ixodes ticks found in Europe, the former Soviet Union, and Asia. The virus causes tick-borne encephalitis. Most patients are asymptomatic; however, symptomatic individuals may experience a biphasic illness. Tick-borne Encephalitis Virus): vírus de RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure de cadeia simples de sentido positivo do género Flavivirus Flavivirus A genus of flaviviridae containing several subgroups and many species. Most are arboviruses transmitted by mosquitoes or ticks. The type species is yellow fever virus. Tick-borne Encephalitis Virus, causando encefalite. A transmissão ocorre sobretudo por carraças Ixodes, e as infeções são comuns na Europa, Rússia e Ásia. A maioria dos doentes é assintomática; no entanto, os indivíduos sintomáticos podem apresentar uma doença bifásica. Após a recuperação dos sintomas inespecíficos, os doentes podem desenvolver manifestações neurológicas como meningite, encefalite ou meningoencefalite. A serologia ou um PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) podem confirmar o diagnóstico. Não existem fármacos antivíricos eficazes para tratar infeções por TBEV TBEV Tick-borne encephalitis virus (TBEV) is a positive-sense, single-stranded RNA virus of the genus Flavivirus. Transmission occurs primarily via Ixodes ticks found in Europe, the former Soviet Union, and Asia. The virus causes tick-borne encephalitis. Most patients are asymptomatic; however, symptomatic individuals may experience a biphasic illness. Tick-borne Encephalitis Virus. O tratamento é de suporte.
  • Vírus da dengue Dengue An acute febrile disease transmitted by the bite of aedes mosquitoes infected with dengue virus. It is self-limiting and characterized by fever, myalgia, headache, and rash. Severe dengue is a more virulent form of dengue. Dengue Virus: pequeno vírus ssRNA de sentido positivo do género Flavivirus Flavivirus A genus of flaviviridae containing several subgroups and many species. Most are arboviruses transmitted by mosquitoes or ticks. The type species is yellow fever virus. Tick-borne Encephalitis Virus. A transmissão ocorre pela picada da fêmea do mosquito Aedes. A maioria das infeções é assintomática. Os indivíduos sintomáticos podem passar por 3 estadios, com manifestações graves se infeção prévia. A fase febril apresenta-se com febre, cefaleias e dor retro-orbitária, mialgias e artralgias (dor “quebra-osso”) e exantema maculopapular Maculopapular Dermatologic Examination. A fase crítica inclui hemorragia e choque. Na fase de convalescença há resolução dos sintomas. O diagnóstico é feito com base nos achados clínicos, serologia, teste de antigénio ou PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR). O tratamento é de suporte.

Referências

  1. Ayoade, F., Cordova, L. (2024) California Encephalitis. Medscape. Retrieved December 8, 2024, from https://emedicine.medscape.com/article/234159-overview#a6
  2. Barbosa, N., Concha, J., Dasilva, L. (2020). Bunyavirus. 10.1016/B978-0-12-818731-9.00037-9. 
  3. Chandy, S., Mathai, D. (2017). Globally emerging hantaviruses: An overview. Indian J Med Microbiol. 35(2), 165-175. https://pubmed.ncbi.nlm.nih.gov/28681802/
  4. Cennimo, D., Hale, Z. (2024). Hantavirus Pulmonary Syndrome. Medscape. Retrieved December 8, 2024, from https://emedicine.medscape.com/article/236425-overview
  5. Drebot, M.A., Jones, S., Grolla, A., Safronetz, D., Strong, J.E., Kobinger, G., Lindsay, R.L. (2015). Hantavirus pulmonary syndrome in Canada: An overview of clinical features, diagnostics, epidemiology, and prevention. Can Commun Dis Rep. 04;41(6), 124-131. https://pubmed.ncbi.nlm.nih.gov/29769944/
  6. Hjelle, B. (2024) Hantavirus cardiopulmonary syndrome. UpToDate. Retrieved December 8, 2024, from https://www.uptodate.com/contents/hantavirus-cardiopulmonary-syndrome
  7. Krause, A., Mirazimi, A. (2010). Molecular biology and pathogenesis of Crimean-Congo hemorrhagic virus. Medscape. Retrieved May 25, 2021, from https://www.medscape.com/viewarticle/729785_2
  8. Leblebicioglu, H. (2024). Crimean-Congo hemorrhagic fever. UpToDate. Retrieved December 8, 2024, from https://www.uptodate.com/contents/crimean-congo-hemorrhagic-fever
  9. Mustonen, J. (2024). Kidney involvement in Hantavirus infections. UpToDate. Retrieved December 8, 2024, from https://www.uptodate.com/contents/kidney-involvement-in-hantavirus-infections
  10. Pepin, M., Bouloy, M., Bird, B.H., Kemp, A., Paweska, J. (2010). Rift Valley fever virus (Bunyaviridae: Phlebovirus): An update on pathogenesis, molecular epidemiology, vectors, diagnostics, and prevention. Vet Res 41, 61.
  11. Petersen, L. (2024). Arthropod-borne encephalitides. UpToDate. Retrieved December 8, 2024, from https://www.uptodate.com/contents/arthropod-borne-encephalitides
  12. Riedel, S., & Hobden, J.A., & Miller, S., & Morse, S.A., & Mietzner, T.A., & Detrick, B., & Mitchell, T.G., & Sakanari, J.A., & Hotez, P., & Mejia, R. (Eds.) (2019). Arthropod-borne and rodent-borne viral diseases. Jawetz, Melnick, & Adelberg’s Medical Microbiology, 28e. McGraw-Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=2629&sectionid=217774914
  13. Sah, R., Mohanty, A., Rohilla, R., Padhi, B. K., Chandran, D., Chakraborty, C., & Dhama, K. (2022). Recent outbreaks of hantavirus—a very lethal and zoonotic virus: An update and counteracting strategies. International Journal of Surgery Open, 49, Article 100582. https://doi.org/10.1016/j.ijso.2022.100582 
  14. Centers for Disease Control and Prevention. (2024). Reported cases of hantavirus disease. Retrieved December 8, 2024, from https://www.cdc.gov/hantavirus/data-research/cases/index.html

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