RESUMO
Some monoclonal antibodies (mAbs) recovered from survivors of filovirus infections can protect against infection. It is currently unknown whether natural infection also induces some antibodies with the capacity for antibody-dependent enhancement (ADE). A panel of mAbs obtained from human survivors of filovirus infection caused by Ebola, Bundibugyo, or Marburg viruses was evaluated for their ability to facilitate ADE. ADE was observed readily with all mAbs examined at sub-neutralizing concentrations, and this effect was not restricted to mAbs with a particular epitope specificity, neutralizing capacity, or subclass. Blocking of specific Fcγ receptors reduced but did not abolish ADE that was associated with high-affinity binding antibodies, suggesting that lower-affinity interactions still cause ADE. Mutations of Fc fragments of an mAb that altered its interaction with Fc receptors rendered the antibody partially protective in vivo at a low dose, suggesting that ADE counteracts antibody-mediated protection and facilitates dissemination of filovirus infections.
Assuntos
Anticorpos Monoclonais/farmacologia , Anticorpos Neutralizantes/farmacologia , Anticorpos Antivirais/farmacologia , Anticorpos Facilitadores , Doença pelo Vírus Ebola/virologia , Doença do Vírus de Marburg/virologia , Animais , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Neutralizantes/isolamento & purificação , Anticorpos Antivirais/isolamento & purificação , Ebolavirus/efeitos dos fármacos , Ebolavirus/genética , Ebolavirus/imunologia , Ebolavirus/patogenicidade , Epitopos/genética , Epitopos/imunologia , Expressão Gênica , Genes Reporter , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/mortalidade , Doença pelo Vírus Ebola/terapia , Humanos , Soros Imunes/química , Fragmentos Fc das Imunoglobulinas/química , Fragmentos Fc das Imunoglobulinas/genética , Doença do Vírus de Marburg/imunologia , Doença do Vírus de Marburg/mortalidade , Doença do Vírus de Marburg/terapia , Marburgvirus/efeitos dos fármacos , Marburgvirus/genética , Marburgvirus/patogenicidade , Camundongos , Camundongos Endogâmicos BALB C , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Monócitos/virologia , Cultura Primária de Células , Receptores de IgG/genética , Receptores de IgG/imunologia , Análise de Sobrevida , Sobreviventes , Células THP-1 , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologiaRESUMO
Marburg and Ebola hemorrhagic fevers are severe, systemic viral diseases affecting humans and non-human primates. They are characterized by multiple symptoms such as hemorrhages, fever, headache, muscle and abdominal pain, chills, sore throat, nausea, vomiting and diarrhea. Elevated liver-associated enzyme levels and coagulopathy are also associated with these diseases. Marburg and Ebola hemorrhagic fevers are caused by (Lake victoria) Marburg virus and different species of Ebola viruses, respectively. They are enveloped, single-stranded RNA viruses and belong to the family of filoviridae. Case fatality rates of filovirus disease outbreaks are among the highest reported for any human pathogen, ranging from 25 to 90% or more. Outbreaks of Marburg and Ebola hemorrhagic fever occur in certain regions of equatorial Africa at irregular intervals. Since 2000, the number of outbreaks has increased. In 2014, the biggest outbreak of a filovirus-induced hemorrhagic fever that has been documented so far occurred from March to July 2014 in Guinea, Sierra Leone, Liberia and Nigeria. The outbreak was caused by a new variant of Zaire Ebola-Virus, affected more than 2600 people (stated 20 August) and was associated with case-fatality rates of up to 67% (Guinea). Treatment of Marburg and Ebola hemorrhagic fevers is symptomatic and supportive, licensed antiviral agents are currently not available. Recently, BCX4430, a promising synthetic adenosine analogue with high in vitro and in vivo activity against filoviruses and other RNA viruses, has been described. BCX4430 inhibits viral RNA polymerase activity and protects cynomolgus macaques from Marburg virus infection when administered as late as 48 hours after infection. Nucleic acid-based products, recombinant vaccines and antibodies appear to be less suitable for the treatment of Marburg and Ebola hemorrhagic fevers.
Assuntos
Doença pelo Vírus Ebola/epidemiologia , Doença do Vírus de Marburg/epidemiologia , África/epidemiologia , Animais , Antivirais/uso terapêutico , Diagnóstico Diferencial , Surtos de Doenças , Reservatórios de Doenças , Ebolavirus/classificação , Doença pelo Vírus Ebola/mortalidade , Doença pelo Vírus Ebola/terapia , Doença pelo Vírus Ebola/virologia , Humanos , Doença do Vírus de Marburg/mortalidade , Doença do Vírus de Marburg/terapia , Doença do Vírus de Marburg/virologia , Marburgvirus/classificaçãoRESUMO
Ebolavirus and Marburgvirus, two filoviruses belonging to the Filoviridae family, are among the most virulent pathogens for humans and non-human primates, causing outbreaks of fulminant hemorrhagic fever (HF) in Central African countries with case fatality rates of up to 90%. Fruit bats are the likely reservoir, and human infection occurs through contact with bats or infected large-animal carcasses or by person-to-person contact (through body fluids, medical care, and burial practices). Schematically, clinical manifestations occur in three successive phases and include general, gastrointestinal, and mucocutaneous disorders. Death usually results from hemorrhagic complications. Cutaneous manifestations rarely make a major contribution to disease severity but can assist with the diagnosis. Rash, the main cutaneous disorder, is nonspecific and cannot guide the differential diagnosis. Immunohistochemical examination of skin biopsy or necropsy specimens can confirm the diagnosis.
Assuntos
Doença pelo Vírus Ebola/complicações , Doença do Vírus de Marburg/complicações , Dermatopatias/virologia , Animais , Ebolavirus , Doença pelo Vírus Ebola/diagnóstico , Doença pelo Vírus Ebola/terapia , Humanos , Doença do Vírus de Marburg/diagnóstico , Doença do Vírus de Marburg/terapia , Marburgvirus , Dermatopatias/patologiaRESUMO
A woman developed Marburg haemorrhagic fever in the Netherlands, most likely as a consequence of being exposed to virus-infected bats in the python cave in Maramagambo Forest during a visit to Uganda. The clinical syndrome was dominated by acute liver failure with secondary coagulopathy, followed by a severe systemic inflammatory response, multiorgan failure, and fatal cerebral oedema. A high blood viral load persisted during the course of the disease. The initial systemic inflammatory response coincided with peaks in interferon-γ and tumour necrosis factor-α concentrations in the blood. A terminal rise in interleukin-6, placental growth factor (PlGF), and soluble vascular endothelial growth factor receptor-1 (sVEGF-R1) seemed to suggest an advanced pathophysiological stage of Marburg haemorrhagic fever associated with vascular endothelial dysfunction and fatal cerebral oedema. The excess of circulating sVEGF-R1 and the high sVEGF-R1:PlGF ratio shortly before death resemble pathophysiological changes thought to play a causative part in pre-eclampsia. Aggressive critical-care treatment with renal replacement therapy and use of the molecular absorbent recirculation system appeared able to stabilise--at least temporarily--the patient's condition.
Assuntos
Doença do Vírus de Marburg/sangue , Doença do Vírus de Marburg/complicações , Adulto , Animais , Edema Encefálico/virologia , Evolução Fatal , Feminino , Humanos , Interleucina-1/sangue , Falência Hepática Aguda/virologia , Doença do Vírus de Marburg/terapia , Insuficiência de Múltiplos Órgãos/virologia , Fator de Crescimento Placentário , Proteínas da Gravidez/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangueRESUMO
BACKGROUND: Plasma exchange (PE) is used to treat severe episodes of CNS demyelination unresponsive to corticosteroids. Predictors of long-term response are not well known. METHODS: We retrospectively reviewed the medical records of 41 patients consecutively treated by PE between January 1995 and July 2007. The primary outcome was improvement at 6 months after PE defined as decrease of >or=1 point in the Expanded Disability Status Scale (EDSS) score for patients with EDSS
Assuntos
Encéfalo/patologia , Doenças Desmielinizantes/terapia , Troca Plasmática/estatística & dados numéricos , Medula Espinal/patologia , Doença Aguda/terapia , Adolescente , Adulto , Animais , Encéfalo/fisiopatologia , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/fisiopatologia , Avaliação da Deficiência , Progressão da Doença , Feminino , Humanos , Masculino , Doença do Vírus de Marburg/patologia , Doença do Vírus de Marburg/fisiopatologia , Doença do Vírus de Marburg/terapia , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Esclerose Múltipla/fisiopatologia , Esclerose Múltipla/terapia , Mielite Transversa/patologia , Mielite Transversa/fisiopatologia , Mielite Transversa/terapia , Neuromielite Óptica/patologia , Neuromielite Óptica/fisiopatologia , Neuromielite Óptica/terapia , Troca Plasmática/métodos , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medula Espinal/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
The paper provides data on the effect of tumor necrosis factor (TNF) antiserum on the course of experimental Marburg hemorrhagic fever. On day 3 of the challenge of guinea pigs with the Popp strain of Marburg virus, the infection event was confirmed by PCR. On days 4-7, the infected animals intramuscularly received a TNF-alpha antiserum. The treated animals showed a 50% survival while all control animals died. It may be assumed that a course of death due to Marburg hemorrhagic fever in shocks brought about by inflammatory cytokines. Therefore, attempts may be made to treat this infection by using the drugs that are TNF antagonists.
Assuntos
Soros Imunes/farmacologia , Imunização Passiva , Doença do Vírus de Marburg/terapia , Fator de Necrose Tumoral alfa/imunologia , Animais , Anticorpos Antivirais/imunologia , Eletroforese em Gel de Ágar , Seguimentos , Cobaias , Humanos , Doença do Vírus de Marburg/metabolismo , Marburgvirus/genética , Marburgvirus/imunologia , Reação em Cadeia da Polimerase , RNA Viral/análise , Resultado do TratamentoRESUMO
Presents data on changes in nonspecific immunity (interferon, tumor necrosis factor, natural killers), spontaneous and mitogen-induced lymphocyte proliferation in the course of development of experimental Marburg fever. Demonstrates the effects of the said factors and interleukin-2 on the course of the fever and their role in a lethal outcome of the disease.