Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 896
Filtrar
1.
Rev Sci Tech ; 38(1): 113-122, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31564736

RESUMO

The natural ecology of Ebola virus infection remains enigmatic. No clear reservoir species has been confirmed but there is evidence of infection in a wide spectrum of mammals, including humans, non-human primates, domestic and wild ungulates and a variety of bat species, both frugivorous and insectivorous. Humans and most other species examined appear to be spillover hosts and suffer disease. Bats are the exception and are tolerant to infection in some laboratory studies. Some surveys show a low prevalence of antibodies against Zaire Ebola virus (ZEBOV) strains in bats during human outbreaks and inter-epidemic periods, and this order of mammals is considered to be the likely reservoir for the virus. Other putative sources include insects but this hypothesis is unproven in the field or laboratory. Moreover, some potential sources, such as aquatic species, have yet to be investigated. There are a number of environmental, human behavioural and ecological risk factors proposed with respect to spillover and spread. In the West African outbreak, which was unprecedented in scale and geographic spread, the source of the spillover remains unproven, although an association exists between the proposed index case and a colony of insectivorous bats. In all but a few Ebola virus disease events, spillover has only been superficially investigated and this was also the case in the West African epidemic. The authors suggest that, to address risks at the human-animal-environmental interface, using a One Health approach, more effort is needed to investigate spillover factors at the time of a ZEBOV epidemic, in addition to conducting inter-epidemic surveys in peridomestic environments. The true prevalence of ZEBOV infection in any species of bats remains unknown. Large-scale, expensive, non-randomised surveys, with low sampling numbers per species, are unlikely to provide evidence for Ebola virus reservoirs or to improve our epidemiological understanding.


Assuntos
Ebolavirus , Doença pelo Vírus Ebola , África Ocidental/epidemiologia , Animais , Quirópteros/virologia , Surtos de Doenças/prevenção & controle , Reservatórios de Doenças , Ebolavirus/fisiologia , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/virologia , Humanos
4.
Pharm Res ; 36(7): 104, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101988

RESUMO

PURPOSE: Since the 2014 Ebola virus (EBOV) outbreak in West Africa there has been considerable effort towards developing drugs to treat Ebola virus disease and yet to date there is no FDA approved treatment. This is important as at the time of writing this manuscript there is an ongoing outbreak in the Democratic Republic of the Congo which has killed over 1000. METHODS: We have evaluated a small number of natural products, some of which had shown antiviral activity against other pathogens. This is exemplified with eugenol, which is found in high concentrations in multiple essential oils, and has shown antiviral activity against feline calicivirus, tomato yellow leaf curl virus, Influenza A virus, Herpes Simplex virus type 1 and 2, and four airborne phages. RESULTS: Four compounds possessed EC50 values less than or equal to 11 µM. Of these, eugenol, had an EC50 of 1.3 µM against EBOV and is present in several plants including clove, cinnamon, basil and bay. Eugenol is much smaller and structurally unlike any compound that has been previously identified as an inhibitor of EBOV, therefore it may provide new mechanistic insights. CONCLUSION: This compound is readily accessible in bulk quantities, is inexpensive, and has a long history of human consumption, which endorses the idea for further assessment as an antiviral therapeutic. This work also suggests that a more exhaustive assessment of natural product libraries against EBOV and other viruses is warranted to improve our ability to identify compounds that are so distinct from FDA approved drugs.


Assuntos
Antivirais/farmacologia , Produtos Biológicos/farmacologia , Ebolavirus/efeitos dos fármacos , Eugenol/farmacologia , Doença pelo Vírus Ebola/tratamento farmacológico , Doença pelo Vírus Ebola/virologia , Células HeLa , Humanos
5.
BMC Infect Dis ; 19(1): 376, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31046707

RESUMO

BACKGROUND: Management of Ebola virus disease (EVD) has historically focused on infection prevention, case detection and supportive care. Several specific anti-Ebola therapies have been investigated, including during the 2014-2016 West African outbreak. Our objective was to conduct a systematic review of the effect of anti-Ebola virus therapies on clinical outcomes to guide their potential use and future evaluation. METHODS: We searched PubMed, EMBASE, Global Health, Cochrane Library, African Index Medicus, WHOLIS (inception-9 April 2018), and trial registries for observational studies or clinical trials, in any language, that enrolled patients with confirmed EVD who received therapy targeting Ebola virus and reported on mortality, symptom duration, or adverse effects. RESULTS: From 11,257 citations and registered trials, we reviewed 55 full-text citations, of which 35 met eligibility criteria (1 randomized clinical trial (RCT), 8 non-randomized comparative studies, 9 case series and 17 case reports) and collectively examined 21 anti-Ebola virus agents. The 31 studies performed during the West African outbreak reported on 4.8% (1377/28616) of all patients with Ebola. The only RCT enrolled 72 patients (0.25% of all patients with Ebola) and compared the monoclonal antibody ZMapp vs. standard care (mortality, 22% vs. 37%; 95% confidence interval for risk difference, - 36 to 7%). Studies of convalescent plasma, interferon-ß-1a, favipiravir, brincidofovir, artesunate-amodiaquine and TKM-130803 were associated with at least moderate risk of bias. CONCLUSIONS: Research evaluating anti-Ebola virus agents has reached very few patients with EVD, and inferences are limited by non-randomized study designs. ZMapp has the most promising treatment signal.


Assuntos
Antivirais/uso terapêutico , Doença pelo Vírus Ebola/tratamento farmacológico , Amidas/uso terapêutico , Amodiaquina/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Artemisininas/uso terapêutico , Bases de Dados Factuais , Combinação de Medicamentos , Ebolavirus/isolamento & purificação , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/virologia , Humanos , Pirazinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Nat Commun ; 10(1): 1788, 2019 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-30996276

RESUMO

Three Ebolavirus genus viruses cause lethal disease and lack targeted therapeutics: Ebola virus, Sudan virus and Bundibugyo virus. Monoclonal antibody (mAb) cocktails against the surface glycoprotein (GP) present a potential therapeutic strategy. Here we report two crystal structures of the antibody BDBV223, alone and complexed with its GP2 stalk epitope, an interesting site for therapeutic/vaccine design due to its high sequence conservation among ebolaviruses. BDBV223, identified in a human survivor of Bundibugyo virus disease, neutralizes both Bundibugyo virus and Ebola virus, but not Sudan virus. Importantly, the structure suggests that BDBV223 binding interferes with both the trimeric bundle assembly of GP and the viral membrane by stabilizing a conformation in which the monomers are separated by GP lifting or bending. Targeted mutagenesis of BDBV223 to enhance SUDV GP recognition indicates that additional determinants of antibody binding likely lie outside the visualized interactions, and perhaps involve quaternary assembly or membrane-interacting regions.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Ebolavirus/efeitos dos fármacos , Doença pelo Vírus Ebola/imunologia , Anticorpos Monoclonais/química , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Monoclonais/metabolismo , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/isolamento & purificação , Anticorpos Neutralizantes/metabolismo , Anticorpos Antivirais/química , Anticorpos Antivirais/isolamento & purificação , Anticorpos Antivirais/metabolismo , Reações Cruzadas/imunologia , Cristalografia por Raios X , Ebolavirus/imunologia , Epitopos/química , Epitopos/imunologia , Doença pelo Vírus Ebola/sangue , Doença pelo Vírus Ebola/virologia , Humanos , Hibridomas , Mutagênese , Sobreviventes , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/imunologia , Proteínas do Envelope Viral/metabolismo
8.
PLoS Negl Trop Dis ; 13(2): e0007185, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30811388

RESUMO

BACKGROUND: While qualitative assessments of Ebola virus disease (EVD)-related stigma have been undertaken among survivors and the general public, quantitative tools and assessment targeting survivors have been lacking. METHODS AND FINDINGS: Beginning in June 2015, EVD survivors from seven Liberian counties, where most of the country's EVD cases occurred, were eligible to enroll in a longitudinal cohort. Seven stigma questions were adapted from the People Living with HIV Stigma Index and asked to EVD survivors over the age of 12 at initial visit (median 358 days post-EVD) and 18 months later. Primary outcome was a 7-item EVD-related stigma index. Explanatory variables included age, gender, educational level, pregnancy status, post-EVD hospitalization, referred to medical care and EVD source. Proportional odds logistic regression models and generalized linear mixed-effects models were used to assess stigma at initial visit and over time. The stigma questions were administered to 859 EVD survivors at initial visit and 741 (86%) survivors at follow-up. While 63% of survivors reported any stigma at initial visit, only 5% reported any stigma at follow-up. Over the 18-month period, there was a significant decrease in stigma among EVD survivors (Adjusted Odds Ratio [AOR], 0.02; 95% Confidence Interval [CI], 0.01-0.04). At initial visit, having primary, junior high or vocational education, and being referred to medical care was associated with higher odds of stigma (educational level: AOR, 1.82; 95%CI, 1.27-2.62; referred: AOR, 1.50; 95%CI, 1.16-1.94). Compared to ages of 20-29, those who had ages of 12-19 or 50+ experienced lower odds of stigma (12-19: AOR, 0.32; 95%CI, 0.21-0.48; 50+: AOR, 0.58 95%CI, 0.37-0.91). CONCLUSIONS: Our data suggest that EVD-related stigma was much lower more than a year after active Ebola transmission ended in Liberia. Among survivors who screened negative for stigma, additional probing may be considered based on age, education, and referral to care.


Assuntos
Doença pelo Vírus Ebola/epidemiologia , Estigma Social , Sobreviventes/estatística & dados numéricos , Adolescente , Adulto , Estudos de Coortes , Surtos de Doenças , Feminino , Doença pelo Vírus Ebola/virologia , Humanos , Libéria/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Gravidez , Inquéritos e Questionários , Sobreviventes/psicologia , Adulto Jovem
9.
Viruses ; 11(2)2019 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-30781518

RESUMO

Following the largest Ebola virus disease outbreak from 2013 to 2016, viral RNA has been detected in survivors from semen and breast milk long after disease recovery. However, as there have been few cases of sexual transmission, it is unclear whether every RNA positive fluid sample contains infectious virus. Virus isolation, typically using cell culture or animal models, can serve as a tool to determine the infectivity of patient samples. However, the sensitivity of these methods has not been assessed for the Ebola virus isolate, Makona. Described here is an efficiency comparison of Ebola virus Makona isolation using Vero E6, Huh-7, monocyte-derived macrophage cells, and suckling laboratory mice. Isolation sensitivity was similar in all methods tested. Laboratory mice and Huh-7 cells were less affected by toxicity from breast milk than Vero E6 and MDM cells. However, the advantages associated with isolation in Huh-7 cells over laboratory mice, including cost effectiveness, sample volume preservation, and a reduction in animal use, make Huh-7 cells the preferred substrate tested for Ebola virus Makona isolation.


Assuntos
Ebolavirus/isolamento & purificação , Virologia/métodos , Animais , Animais Lactentes , Linhagem Celular , Linhagem Celular Tumoral , Cercopithecus aethiops , Doença pelo Vírus Ebola/virologia , Humanos , Macrófagos/virologia , Camundongos , Camundongos Endogâmicos BALB C , Leite Humano/virologia , Sêmen/virologia , Sensibilidade e Especificidade , Células Vero
10.
Proc Natl Acad Sci U S A ; 116(9): 3919-3928, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30808769

RESUMO

Ebola virus disease (EVD) often leads to severe and fatal outcomes in humans with early supportive care increasing the chances of survival. Profiling the human plasma lipidome provides insight into critical illness as well as diseased states, as lipids have essential roles as membrane structural components, signaling molecules, and energy sources. Here we show that the plasma lipidomes of EVD survivors and fatalities from Sierra Leone, infected during the 2014-2016 Ebola virus outbreak, were profoundly altered. Focusing on how lipids are associated in human plasma, while factoring in the state of critical illness, we found that lipidome changes were related to EVD outcome and could identify states of disease and recovery. Specific changes in the lipidome suggested contributions from extracellular vesicles, viremia, liver dysfunction, apoptosis, autophagy, and general critical illness, and we identified possible targets for therapies enhancing EVD survival.


Assuntos
Estado Terminal/epidemiologia , Doença pelo Vírus Ebola/genética , Metabolismo dos Lipídeos/genética , Lipídeos/genética , Adolescente , Adulto , Criança , Surtos de Doenças , Ebolavirus/genética , Ebolavirus/patogenicidade , Feminino , Regulação da Expressão Gênica/genética , Doença pelo Vírus Ebola/sangue , Doença pelo Vírus Ebola/patologia , Doença pelo Vírus Ebola/virologia , Humanos , Lipídeos/sangue , Masculino , Serra Leoa/epidemiologia , Adulto Jovem
11.
Cell Host Microbe ; 25(1): 39-48.e5, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30629917

RESUMO

Passive administration of monoclonal antibodies (mAbs) is a promising therapeutic approach for Ebola virus disease (EVD). However, all mAbs and mAb cocktails that have entered clinical development are specific for a single member of the Ebolavirus genus, Ebola virus (EBOV), and ineffective against outbreak-causing Bundibugyo virus (BDBV) and Sudan virus (SUDV). Here, we advance MBP134, a cocktail of two broadly neutralizing human mAbs, ADI-15878 from an EVD survivor and ADI-23774 from the same survivor but specificity-matured for SUDV GP binding affinity, as a candidate pan-ebolavirus therapeutic. MBP134 potently neutralized all ebolaviruses and demonstrated greater protective efficacy than ADI-15878 alone in EBOV-challenged guinea pigs. A second-generation cocktail, MBP134AF, engineered to effectively harness natural killer (NK) cells afforded additional improvement relative to its precursor in protective efficacy against EBOV and SUDV in guinea pigs. MBP134AF is an optimized mAb cocktail suitable for evaluation as a pan-ebolavirus therapeutic in nonhuman primates.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Ebolavirus/imunologia , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/prevenção & controle , Bem-Estar do Animal , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/isolamento & purificação , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/administração & dosagem , Anticorpos Antivirais/uso terapêutico , Antivirais , Modelos Animais de Doenças , Ebolavirus/patogenicidade , Epitopos/imunologia , Feminino , Filoviridae/imunologia , Cobaias , Doença pelo Vírus Ebola/virologia , Humanos , Imunoterapia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Proteínas Recombinantes/imunologia , Resultado do Tratamento
12.
Cell Host Microbe ; 25(1): 10-12, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30629912

RESUMO

Pan-Ebolavirus immunotherapy would provide a rapid-response treatment during Ebola virus outbreaks. In this issue of Cell Host & Microbe, Wec et al. (2019) and Bornholdt et al. (2019) optimize the MBP134 mAb cocktail through antibody affinity maturation, improving its protective efficacy against three Ebolaviruses: EBOV, SUDV, and BDBV.


Assuntos
Ebolavirus , Doença pelo Vírus Ebola/virologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Modelos Animais de Doenças , Humanos
14.
Zoonoses Public Health ; 66(3): 288-295, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30677236

RESUMO

The ecology of Ebola virus (EBV) remains largely unknown, but the previous detection of viral RNA and anti-EBV antibodies in African bats suggests that they might play a role in the EBV reservoir. Moreover, African bats also carry other potentially zoonotic agents such as Henipah-like viruses, coronaviruses and lyssaviruses. Today only little information is available on interactions between humans and bats. The objective of our exploratory study was to describe the extent and modes of contacts between humans and bats in southern Cameroon, considered as an area at risk for future EBV outbreaks. The survey was conducted in 11 villages of four distinct rural areas in southern Cameroon. A total of 135 respondents were interviewed using semi-structured questionnaires, between February and May 2017. The study showed that direct contacts between bats and humans are relatively common. Bat bushmeat appeared to be an occasional meat resource; 40% of respondents consume bats with a median annual consumption of three, and 28% of respondents hunt them. About 22% of the respondents reported children catching bats. Indirect contact also appeared to be common; 55% of hunters use caves as shelters and 67% of interviewees eat fruits previously chewed by bats. Bat consumption varied significantly between regions (from 0% to 87%) and between pygmies and bantus in the extreme south-east of Cameroon. The study revealed considerable diversity in practices among interviewees, most of them being subsistence cultivators and relying on self-hunted bushmeat. Geographical diversity of contacts and perceptions regarding bats in Cameroon emphasizes the need to adjust zoonotic pathogen surveillance and education campaigns to the specificities of the communities and their context of interaction with wildlife.


Assuntos
Quirópteros/virologia , Ebolavirus/fisiologia , Doença pelo Vírus Ebola/virologia , Zoonoses , Animais , Camarões/epidemiologia , Coleta de Dados , Conhecimentos, Atitudes e Prática em Saúde , Doença pelo Vírus Ebola/transmissão , Humanos , Inquéritos e Questionários
15.
BMC Infect Dis ; 19(1): 81, 2019 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-30678649

RESUMO

BACKGROUND: The West Africa Ebola Virus Disease (EVD) outbreak in 2014-2016 was declared by the World Health Organization (WHO) a public health emergency of international concern. Most of the previous studies done in Sierra Leone relating to the clinical and epidemiological features of EVD during the 2014-2016 West African outbreak focused on adult EVD patients. There have been conflicting reports about the effects of EVD on children during previous outbreaks. METHODS: This is an observational retrospective analysis of medical data of all laboratory confirmed paediatric EVD patients below 15 years of age who were admitted at the 34 Military Hospital Ebola Treatment Center (ETC) in Wilberforce, Sierra Leone between June 2014 to April 2015. We analyzed the sociodemographic and clinical characteristics of paediatric EVD cases contained in case report forms that were collected by Ebola surveillance officers and clinicians at the 34 Military Hospital ETC. Both univariate and multivariate logistic regression models were used to determine the sociodemographic and clinical characteristics of paediatric EVD patients that were associated with EVD facility-based mortality. RESULTS: The majority of the paediatric EVD cases in this study were female (56.1%), pupils (51.1%), and 43.2% belonged to the age group between 10 years and below 15 years. The median age of the paediatric EVD cases was 9 years (interquartile range = 4 to 11 years). Adjusting for other covariates in the model, male paediatric EVD patient (AOR = 13.4, 95% CI = [2.07-156-18], p <  0.05), EVD patient with abdominal pain (AOR = 11.0, 95% CI = [1.30-161.81], p <  0.05), vomiting (AOR = 35.7, 95% CI = [3.43-833.73], p <  0.05), signs of conjunctivitis (AOR = 17.4, 95% CI = [1.53-342.21], p <  0.05) and difficulty in breathing (AOR = 23.3, 95% CI = [1.92-713.01], p <  0.05) at the time of admission had increased odds of dying during EVD treatment. CONCLUSIONS: We recommend the adoption of case definitions currently in vigour to cater for specific characteristics of paediatric patients. Subgroups that can be identified by applying the model developed in this study may require special attention and intensified care.


Assuntos
Doença pelo Vírus Ebola/tratamento farmacológico , Adulto , Antivirais/administração & dosagem , Criança , Pré-Escolar , Surtos de Doenças , Ebolavirus/fisiologia , Feminino , Doença pelo Vírus Ebola/diagnóstico , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/virologia , Hospitalização , Humanos , Modelos Logísticos , Masculino , Pediatria/estatística & dados numéricos , Estudos Retrospectivos , Serra Leoa/epidemiologia , Resultado do Tratamento
16.
Nat Commun ; 10(1): 285, 2019 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-30655525

RESUMO

There are no approved therapies for Ebola virus infection. Here, to find potential therapeutic targets, we perform a screen for genes essential for Ebola virus (EBOV) infection. We identify GNPTAB, which encodes the α and ß subunits of N-acetylglucosamine-1-phosphate transferase. We show that EBOV infection of a GNPTAB knockout cell line is impaired, and that this is reversed by reconstituting GNPTAB expression. Fibroblasts from patients with mucolipidosis II, a disorder associated with mutations in GNPTAB, are refractory to EBOV, whereas cells from their healthy parents support infection. Impaired infection correlates with loss of the expression of cathepsin B, known to be essential for EBOV entry. GNPTAB activity is dependent upon proteolytic cleavage by the SKI-1/S1P protease. Inhibiting this protease with the small-molecule PF-429242 blocks EBOV entry and infection. Disruption of GNPTAB function may represent a strategy for a host-targeted therapy for EBOV.


Assuntos
Antivirais/farmacologia , Ebolavirus/patogenicidade , Doença pelo Vírus Ebola/tratamento farmacológico , Mucolipidoses/patologia , Transferases (Outros Grupos de Fosfato Substituídos)/genética , Internalização do Vírus/efeitos dos fármacos , Células A549 , Animais , Antivirais/uso terapêutico , Catepsina B/metabolismo , Cercopithecus aethiops , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Fibroblastos , Técnicas de Inativação de Genes , Doença pelo Vírus Ebola/virologia , Humanos , Mucolipidoses/genética , Pró-Proteína Convertases/antagonistas & inibidores , Pró-Proteína Convertases/metabolismo , Inibidores de Proteases/farmacologia , Pirrolidinas/farmacologia , Serina Endopeptidases/metabolismo , Transferases (Outros Grupos de Fosfato Substituídos)/antagonistas & inibidores , Células Vero , Sequenciamento Completo do Genoma
17.
DNA Cell Biol ; 38(2): 115-120, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30615471

RESUMO

Ebola virus (EBOV) is an enveloped filamentous virus that causes severe hemorrhagic fever in humans and nonhuman primates with up to 90% fatality. Accumulating evidence indicates that various viruses, including EBOV, exploit the host apoptotic clearance machinery to enhance their entry into host cells by externalizing phosphatidylserine (PS) in the viral envelope. PS is typically distributed in the inner layer of the plasma membrane (PM) in normal cells. Progeny EBOV virions bud from the PM of infected cells, suggesting that PS is likely flipped to the outer leaflet of the envelope of Ebola virions. Currently, the intracellular dynamics of PS during EBOV infection are poorly understood. This review summarizes recent progress in determining the molecular mechanism of externalization of PS in the envelope of EBOV particles. We also discuss future directions and how viral apoptotic mimicry could be targeted for therapeutics.


Assuntos
Ebolavirus/metabolismo , Fosfatidilserinas/metabolismo , Proteínas do Envelope Viral/metabolismo , Animais , Membrana Celular/virologia , Doença pelo Vírus Ebola/virologia , Humanos , Vírion/metabolismo
18.
Emerg Infect Dis ; 25(2): 290-298, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30666927

RESUMO

Ebola virus disease (EVD) is associated with elevated cytokine levels, and hypercytokinemia is more pronounced in fatal cases. This type of hyperinflammatory state is reminiscent of 2 rheumatologic disorders known as macrophage activation syndrome and hemophagocytic lymphohistiocytosis, which are characterized by macrophage and T-cell activation. An evaluation of 2 cohorts of patients with EVD revealed that a marker of macrophage activation (sCD163) but not T-cell activation (sCD25) was associated with severe and fatal EVD. Furthermore, substantial immunoreactivity of host tissues to a CD163-specific antibody, predominantly in areas of extensive immunostaining for Ebola virus antigens, was observed in fatal cases. These data suggest that host macrophage activation contributes to EVD pathogenesis and that directed antiinflammatory therapies could be beneficial in the treatment of EVD.


Assuntos
Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Ebolavirus/imunologia , Doença pelo Vírus Ebola/sangue , Doença pelo Vírus Ebola/imunologia , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Receptores de Superfície Celular/sangue , Biomarcadores , Doença pelo Vírus Ebola/diagnóstico , Doença pelo Vírus Ebola/virologia , Humanos , Imunoensaio , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Macrófagos/metabolismo
19.
Cell Host Microbe ; 25(1): 49-58.e5, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30629918

RESUMO

Recent and ongoing outbreaks of Ebola virus disease (EVD) underscore the unpredictable nature of ebolavirus reemergence and the urgent need for antiviral treatments. Unfortunately, available experimental vaccines and immunotherapeutics are specific for a single member of the Ebolavirus genus, Ebola virus (EBOV), and ineffective against other ebolaviruses associated with EVD, including Sudan virus (SUDV) and Bundibugyo virus (BDBV). Here we show that MBP134AF, a pan-ebolavirus therapeutic comprising two broadly neutralizing human antibodies (bNAbs), affords unprecedented effectiveness and potency as a therapeutic countermeasure to antigenically diverse ebolaviruses. MBP134AF could fully protect ferrets against lethal EBOV, SUDV, and BDBV infection, and a single 25-mg/kg dose was sufficient to protect NHPs against all three viruses. The development of MBP134AF provides a successful model for the rapid discovery and translational advancement of immunotherapeutics targeting emerging infectious diseases.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/uso terapêutico , Ebolavirus/patogenicidade , Furões/virologia , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/prevenção & controle , Bem-Estar do Animal , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/isolamento & purificação , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/administração & dosagem , Linhagem Celular , Cercopithecus aethiops , Modelos Animais de Doenças , Feminino , Filoviridae/imunologia , Infecções por Filoviridae/imunologia , Infecções por Filoviridae/prevenção & controle , Infecções por Filoviridae/virologia , Glicoproteínas/imunologia , Cobaias , Células HEK293 , Doença pelo Vírus Ebola/virologia , Humanos , Células Matadoras Naturais , Macaca , Macaca fascicularis , Masculino , Primatas , Análise de Sobrevida , Resultado do Tratamento , Proteínas Virais/imunologia
20.
Emerg Infect Dis ; 25(2): 249-255, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30500321

RESUMO

Ebola virus (EBOV) can persist in immunologically protected body sites in survivors of Ebola virus disease, creating the potential to initiate new chains of transmission. From the outbreak in West Africa during 2014-2016, we identified 13 possible events of viral persistence-derived transmission of EBOV (VPDTe) and applied predefined criteria to classify transmission events based on the strength of evidence for VPDTe and source and route of transmission. For 8 events, a recipient case was identified; possible source cases were identified for 5 of these 8. For 5 events, a recipient case or chain of transmission could not be confidently determined. Five events met our criteria for sexual transmission (male-to-female). One VPDTe event led to at least 4 generations of cases; transmission was limited after the other events. VPDTe has increased the importance of Ebola survivor services and sustained surveillance and response capacity in regions with previously widespread transmission.


Assuntos
Surtos de Doenças , Ebolavirus , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/transmissão , Sobreviventes , Adolescente , Adulto , África Ocidental/epidemiologia , Ebolavirus/classificação , Ebolavirus/genética , Ebolavirus/isolamento & purificação , Feminino , Doença pelo Vírus Ebola/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância em Saúde Pública , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA