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2.
MMWR Morb Mortal Wkly Rep ; 68(50): 1162-1165, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31856146

RESUMO

On August 1, 2018, the Democratic Republic of the Congo Ministry of Health (DRC MoH) declared the tenth outbreak of Ebola virus disease (Ebola) in DRC, in the North Kivu province in eastern DRC on the border with Uganda, 8 days after another Ebola outbreak was declared over in northwest Équateur province. During mid- to late-July 2018, a cluster of 26 cases of acute hemorrhagic fever, including 20 deaths, was reported in North Kivu province.* Blood specimens from six patients hospitalized in the Mabalako health zone and sent to the Institut National de Recherche Biomédicale (National Biomedical Research Institute) in Kinshasa tested positive for Ebola virus. Genetic sequencing confirmed that the outbreaks in North Kivu and Équateur provinces were unrelated. From North Kivu province, the outbreak spread north to Ituri province, and south to South Kivu province (1). On July 17, 2019, the World Health Organization designated the North Kivu and Ituri outbreak a public health emergency of international concern, based on the geographic spread of the disease to Goma, the capital of North Kivu province, and to Uganda and the challenges to implementing prevention and control measures specific to this region (2). This report describes the outbreak in the North Kivu and Ituri provinces. As of November 17, 2019, a total of 3,296 Ebola cases and 2,196 (67%) deaths were reported, making this the second largest documented outbreak after the 2014-2016 epidemic in West Africa, which resulted in 28,600 cases and 11,325 deaths.† Since August 2018, DRC MoH has been collaborating with partners, including the World Health Organization, the United Nations Children's Fund, the United Nations Office for the Coordination of Humanitarian Affairs, the International Organization of Migration, The Alliance for International Medical Action (ALIMA), Médecins Sans Frontières, DRC Red Cross National Society, and CDC, to control the outbreak. Enhanced communication and effective community engagement, timing of interventions during periods of relative stability, and intensive training of local residents to manage response activities with periodic supervision by national and international personnel are needed to end the outbreak.


Assuntos
Surtos de Doenças , Doença pelo Vírus Ebola/epidemiologia , República Democrática do Congo/epidemiologia , Surtos de Doenças/prevenção & controle , Ebolavirus/isolamento & purificação , Feminino , Doença pelo Vírus Ebola/prevenção & controle , Humanos , Laboratórios , Masculino , Prática de Saúde Pública
4.
N Engl J Med ; 381(24): 2293-2303, 2019 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-31774950

RESUMO

BACKGROUND: Although several experimental therapeutics for Ebola virus disease (EVD) have been developed, the safety and efficacy of the most promising therapies need to be assessed in the context of a randomized, controlled trial. METHODS: We conducted a trial of four investigational therapies for EVD in the Democratic Republic of Congo, where an outbreak began in August 2018. Patients of any age who had a positive result for Ebola virus RNA on reverse-transcriptase-polymerase-chain-reaction assay were enrolled. All patients received standard care and were randomly assigned in a 1:1:1:1 ratio to intravenous administration of the triple monoclonal antibody ZMapp (the control group), the antiviral agent remdesivir, the single monoclonal antibody MAb114, or the triple monoclonal antibody REGN-EB3. The REGN-EB3 group was added in a later version of the protocol, so data from these patients were compared with those of patients in the ZMapp group who were enrolled at or after the time the REGN-EB3 group was added (the ZMapp subgroup). The primary end point was death at 28 days. RESULTS: A total of 681 patients were enrolled from November 20, 2018, to August 9, 2019, at which time the data and safety monitoring board recommended that patients be assigned only to the MAb114 and REGN-EB3 groups for the remainder of the trial; the recommendation was based on the results of an interim analysis that showed superiority of these groups to ZMapp and remdesivir with respect to mortality. At 28 days, death had occurred in 61 of 174 patients (35.1%) in the MAb114 group, as compared with 84 of 169 (49.7%) in the ZMapp group (P = 0.007), and in 52 of 155 (33.5%) in the REGN-EB3 group, as compared with 79 of 154 (51.3%) in the ZMapp subgroup (P = 0.002). A shorter duration of symptoms before admission and lower baseline values for viral load and for serum creatinine and aminotransferase levels each correlated with improved survival. Four serious adverse events were judged to be potentially related to the trial drugs. CONCLUSIONS: Both MAb114 and REGN-EB3 were superior to ZMapp in reducing mortality from EVD. Scientifically and ethically sound clinical research can be conducted during disease outbreaks and can help inform the outbreak response. (Funded by the National Institute of Allergy and Infectious Diseases and others; PALM ClinicalTrials.gov number, NCT03719586.).


Assuntos
Alanina/análogos & derivados , Anticorpos Monoclonais/uso terapêutico , Antivirais/uso terapêutico , Doença pelo Vírus Ebola/tratamento farmacológico , Ribonucleotídeos/uso terapêutico , Adolescente , Adulto , Alanina/efeitos adversos , Alanina/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Antivirais/efeitos adversos , Criança , Pré-Escolar , República Democrática do Congo/epidemiologia , Surtos de Doenças , Ebolavirus/genética , Feminino , Doença pelo Vírus Ebola/mortalidade , Humanos , Lactente , Recém-Nascido , Infusões Intravenosas , Masculino , RNA Viral/sangue , Ribonucleotídeos/efeitos adversos , Método Simples-Cego , Adulto Jovem
5.
BMC Infect Dis ; 19(1): 981, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752717

RESUMO

BACKGROUND: The ninth outbreak of Ebola Virus Disease (EVD) in the Democratic Republic of the Congo occurred in Équateur Province from 8 May-24 July 2018. A system of health facility (HF)-based active case finding (ACF) was implemented in Mbandaka, a regional capital with four confirmed EVD cases, following completion of contact tracing. The goal of this HF-based ACF system was to look for undetected EVD cases among patients that visited HFs beginning one week prior to the system's implementation. METHODS: From 23 June - 24 July 2018, ACF teams visited HFs in Mbandaka and reviewed all medical records as far back as 17 June for any consultations meeting the suspected EVD case definition. The teams then assessed whether to validate these as suspected EVD cases based on factors such as recovery, epidemiological links, and their clinical judgement. ACF teams also assessed HFs' awareness of EVD symptoms and the process for alerting suspected cases. We calculated descriptive statistics regarding the characteristics of reviewed consultations, alert cases, and visited HFs. We also used univariate and multivariate random effects logistic regression models to evaluate the impact of repeated ACF visits to the same HF on the staff's awareness of EVD. RESULTS: ACF teams reviewed 37,746 consultations, of which 690 met the definition of a suspected case of EVD. Two were validated as suspected EVD cases and transferred to the Ebola Treatment Unit for testing; both tested negative. Repeated ACF visits to the same HF were significantly associated with improved EVD awareness (p < 0.001) in univariate and multivariate analyses. CONCLUSION: HF-based ACF during EVD outbreaks may improve EVD awareness and reveal many individuals meeting the suspected case definition. However, many who meet this definition may not have EVD, depending on the population size covered by ACF and amount of ongoing EVD transmission. Given the burdensome procedure of testing suspected EVD cases, future HF-based ACF systems would benefit from improved clarity on which patients require further testing.


Assuntos
Notificação de Doenças/métodos , Doença pelo Vírus Ebola/virologia , República Democrática do Congo/epidemiologia , Surtos de Doenças , Ebolavirus/genética , Ebolavirus/isolamento & purificação , Ebolavirus/fisiologia , Feminino , Instalações de Saúde/estatística & dados numéricos , Doença pelo Vírus Ebola/diagnóstico , Doença pelo Vírus Ebola/epidemiologia , Humanos , Modelos Logísticos , Masculino
7.
Nat Commun ; 10(1): 4531, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615986

RESUMO

Recent outbreaks of animal-borne emerging infectious diseases have likely been precipitated by a complex interplay of changing ecological, epidemiological and socio-economic factors. Here, we develop modelling methods that capture elements of each of these factors, to predict the risk of Ebola virus disease (EVD) across time and space. Our modelling results match previously-observed outbreak patterns with high accuracy, and suggest further outbreaks could occur across most of West and Central Africa. Trends in the underlying drivers of EVD risk suggest a 1.75 to 3.2-fold increase in the endemic rate of animal-human viral spill-overs in Africa by 2070, given current modes of healthcare intervention. Future global change scenarios with higher human population growth and lower rates of socio-economic development yield a fourfold higher likelihood of epidemics occurring as a result of spill-over events. Our modelling framework can be used to target interventions designed to reduce epidemic risk for many zoonotic diseases.


Assuntos
Doenças Transmissíveis Emergentes/virologia , Ebolavirus/fisiologia , Meio Ambiente , Doença pelo Vírus Ebola/virologia , Fatores Socioeconômicos , Zoonoses/virologia , África/epidemiologia , Animais , Doenças Transmissíveis Emergentes/epidemiologia , Surtos de Doenças/prevenção & controle , Epidemias/prevenção & controle , Doença pelo Vírus Ebola/epidemiologia , Humanos , Fatores de Risco , Zoonoses/epidemiologia
9.
Nat Med ; 25(10): 1589-1600, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31591605

RESUMO

Recombinant vesicular stomatitis virus-Zaire Ebola virus (rVSV-ZEBOV) is the most advanced Ebola virus vaccine candidate and is currently being used to combat the outbreak of Ebola virus disease (EVD) in the Democratic Republic of the Congo (DRC). Here we examine the humoral immune response in a subset of human volunteers enrolled in a phase 1 rVSV-ZEBOV vaccination trial by performing comprehensive single B cell and electron microscopy structure analyses. Four studied vaccinees show polyclonal, yet reproducible and convergent B cell responses with shared sequence characteristics. EBOV-targeting antibodies cross-react with other Ebolavirus species, and detailed epitope mapping revealed overlapping target epitopes with antibodies isolated from EVD survivors. Moreover, in all vaccinees, we detected highly potent EBOV-neutralizing antibodies with activities comparable or superior to the monoclonal antibodies currently used in clinical trials. These include antibodies combining the IGHV3-15/IGLV1-40 immunoglobulin gene segments that were identified in all investigated individuals. Our findings will help to evaluate and direct current and future vaccination strategies and offer opportunities for novel EVD therapies.


Assuntos
Vacinas contra Ebola/administração & dosagem , Ebolavirus/imunologia , Doença pelo Vírus Ebola/prevenção & controle , Imunidade Humoral/imunologia , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Formação de Anticorpos/imunologia , Linfócitos B/imunologia , Linfócitos B/virologia , Vacinas contra Ebola/efeitos adversos , Vacinas contra Ebola/imunologia , Ebolavirus/patogenicidade , Feminino , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Vacinação/efeitos adversos , Vesiculovirus/genética , Voluntários
10.
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
11.
Emerg Microbes Infect ; 8(1): 1511-1523, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31631785

RESUMO

Interferons (IFNs) control viral infections by inducing expression of IFN-stimulated genes (ISGs) that restrict distinct steps of viral replication. We report herein that gamma-interferon-inducible lysosomal thiol reductase (GILT), a lysosome-associated ISG, restricts the infectious entry of selected enveloped RNA viruses. Specifically, we demonstrated that GILT was constitutively expressed in lung epithelial cells and fibroblasts and its expression could be further induced by type II interferon. While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins. Furthermore, mutations that impaired the thiol reductase activity or disrupted the N-linked glycosylation, a posttranslational modification essential for its lysosomal localization, largely compromised GILT restriction of viral entry. We also found that the induction of GILT expression reduced the level and activity of cathepsin L, which is required for the entry of these RNA viruses in lysosomes. Our data indicate that GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses.


Assuntos
Ebolavirus/fisiologia , Doença pelo Vírus Ebola/imunologia , Febre Lassa/imunologia , Vírus Lassa/fisiologia , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/imunologia , Vírus da SARS/fisiologia , Síndrome Respiratória Aguda Grave/imunologia , Proteínas do Envelope Viral/metabolismo , Internalização do Vírus , Catepsina L/genética , Catepsina L/imunologia , Linhagem Celular , Ebolavirus/genética , Doença pelo Vírus Ebola/genética , Doença pelo Vírus Ebola/virologia , Humanos , Febre Lassa/genética , Febre Lassa/virologia , Vírus Lassa/genética , Lisossomos/genética , Lisossomos/imunologia , Lisossomos/virologia , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/genética , Vírus da SARS/genética , Síndrome Respiratória Aguda Grave/genética , Síndrome Respiratória Aguda Grave/virologia , Proteínas do Envelope Viral/genética , Replicação Viral
12.
Emerg Microbes Infect ; 8(1): 1347-1360, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31516086

RESUMO

The polymerase complex of Ebola virus (EBOV) is the functional unit for transcription and replication of viral genome. Nucleoprotein (NP) is a multifunctional protein with high RNA binding affinity and recruits other viral proteins to form functional polymerase complex. In our study, we investigated host proteins associated with EBOV polymerase complex using NP as bait in a transcription and replication competent minigenome system by mass spectrometry analysis and identified SET and MYND domain-containing protein 3 (SMYD3) as a novel host protein which was required for the replication of EBOV. SMYD3 specifically interacted with NP and was recruited to EBOV inclusion bodies through NP. The depletion of SMYD3 dramatically suppressed EBOV mRNA production. A mimic of non-phosphorylated VP30, which is a transcription activator, could partially rescue the viral mRNA production downregulated by the depletion of SMYD3. In addition, SMYD3 promoted NP-VP30 interaction in a dose-dependent manner. These results revealed that SMYD3 was a novel host factor recruited by NP to supporting EBOV mRNA transcription through increasing the binding of VP30 to NP. Thus, our study provided a new understanding of mechanism underlying the transcription of EBOV genome, and a novel anti-EBOV drug design strategy by targeting SMYD3.


Assuntos
Ebolavirus/fisiologia , Histona-Lisina N-Metiltransferase/metabolismo , Interações Hospedeiro-Patógeno , Proteínas do Nucleocapsídeo/metabolismo , RNA Mensageiro/biossíntese , RNA Viral/biossíntese , Transcrição Genética , Células HEK293 , Humanos , Espectrometria de Massas , Ligação Proteica , Mapeamento de Interação de Proteínas
13.
PLoS Negl Trop Dis ; 13(9): e0007645, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31504036

RESUMO

BACKGROUND: This study sought understand how the 2014-2016 EVD Virus Disease (EVD) outbreak impacted the nutrition sector in Sierra Leone and use findings for improving nutrition responses during future outbreaks of this magnitude. METHODOLOGY: This qualitative study was iterative and emergent. In-depth interviews (n = 42) were conducted over two phases by purposively sampling both key informants (n = 21; government stakeholders, management staff from United Nations (UN) agencies and non-governmental organizations (NGO)), as well as community informants (n = 21; EVD survivors, health workers, community leaders) until data saturation. Multiple analysts collaborated in a team-based coding approach to identify key themes using Dedoose software. Findings are presented as both quotations and tables/figures. RESULTS: The EVD outbreak effects and the related response strategies, especially movement restriction policies including 21-day quarantines, contributed to disruptions across the food value-chain in Sierra Leone. System-wide impacts were similar to those typically seen in large-scale disasters such as earthquakes. Participants described an array of direct and indirect effects on agricultural production and food storage and processing, as well as on distribution, transport, trade, and retailing. Secondary data were triangulated by interviews which described the aggregate negative effect of this outbreak on key pillars of food security, infant and young child feeding practices, and nutrition. During the humanitarian response, nutrition-specific interventions, including food assistance, were highly accepted, although sharing was reported. Despite EVD impacts across the entire food value-chain, nutrition-sensitive interventions were not central to the initial response as EVD containment and survival took priority. Culturally-appropriate social and behavior change communications were a critical response component for improving health, nutrition, and hygiene-related behaviors through community engagement. CONCLUSIONS: Infectious diseases such as EVD have far-reaching effects that impact health and nutrition through interrelated pathways. In Sierra Leone, the entire food value-chain was broken to the extent that the system-wide damage was on par with that typically resulting from large natural disasters. A food value-chain approach, at minimum, offers a foundational framework from which to position nutrition preparedness and response efforts for outbreaks in similar resource constrained settings.


Assuntos
Surtos de Doenças , Abastecimento de Alimentos , Doença pelo Vírus Ebola , Estado Nutricional , Pré-Escolar , Produção Agrícola , Ebolavirus , Indústria de Processamento de Alimentos , Humanos , Lactente , Pesquisa Qualitativa , Quarentena , Serra Leoa
14.
Molecules ; 24(17)2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31480658

RESUMO

Due to their ability to inhibit viral DNA or RNA replication, nucleoside analogues have been used for decades as potent antiviral therapeutics. However, one of the major limitations of nucleoside analogues is the development of antiviral resistance. In that regard, flexible nucleoside analogues known as "fleximers" have garnered attention over the years due to their ability to survey different amino acids in enzyme binding sites, thus overcoming the potential development of antiviral resistance. Acyclic fleximers have previously demonstrated antiviral activity against numerous viruses including Middle East Respiratory Syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), and, most recently, flaviviruses such as Dengue (DENV) and Yellow Fever Virus (YFV). Due to these interesting results, a Structure Activity Relationship (SAR) study was pursued in order to analyze the effect of the pyrimidine functional group and acyl protecting group on antiviral activity, cytotoxicity, and conformation. The results of those studies are presented herein.


Assuntos
Antivirais/química , Antivirais/farmacologia , Pirimidinas/química , Pirimidinas/farmacologia , Linhagem Celular Tumoral , Ebolavirus/efeitos dos fármacos , Humanos , Indicadores e Reagentes , Lipídeos/química , Conformação Molecular , Espectroscopia de Prótons por Ressonância Magnética , Relação Estrutura-Atividade
16.
PLoS Negl Trop Dis ; 13(8): e0007654, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31369554

RESUMO

The 2013-2016 Ebola virus outbreak in West Africa was the largest and deadliest outbreak to date. Here we conducted a serological study to examine the antibody levels in survivors and the seroconversion in close contacts who took care of Ebola-infected individuals, but did not develop symptoms of Ebola virus disease. In March 2017, we collected blood samples from 481 individuals in Makeni, Sierra Leone: 214 survivors and 267 close contacts. Using commercial, quantitative ELISAs, we tested the plasma for IgG-specific antibodies against three major viral antigens: GP, the only viral glycoprotein expressed on the virus surface; NP, the most abundant viral protein; and VP40, a major structural protein of Zaire ebolavirus. We also determined neutralizing antibody titers. In the cohort of Ebola survivors, 97.7% of samples (209/214) had measurable antibody levels against GP, NP, and/or VP40. Of these positive samples, all but one had measurable neutralizing antibody titers against Ebola virus. For the close contacts, up to 12.7% (34/267) may have experienced a subclinical virus infection as indicated by detectable antibodies against GP. Further investigation is warranted to determine whether these close contacts truly experienced subclinical infections and whether these asymptomatic infections played a role in the dynamics of transmission.


Assuntos
Anticorpos Antivirais/sangue , Ebolavirus/imunologia , Doença pelo Vírus Ebola/imunologia , Sobreviventes , Adulto , Anticorpos Neutralizantes/sangue , Estudos Transversais , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Plasma/imunologia , Serra Leoa , Adulto Jovem
18.
Chem Asian J ; 14(22): 3962-3968, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31389664

RESUMO

Eight different compounds, all nucleoside analogues, could presently be considered as potential drug candidates for the treatment of Ebola virus (EBOV) and/or other hemorrhagic fever virus (HFV) infections. They can be considered as either (i) adenine analogues (3-deazaneplanocin A, galidesivir, GS-6620 and remdesivir) or (ii) guanine analogues containing the carboxamide entity (ribavirin, EICAR, pyrazofurin and favipiravir). All eight owe their mechanism of action to hydrogen bonded base pairing with either (i) uracil or (ii) cytosine. Four out of the eight compounds (galidesivir, GS-6620, remdesivir and pyrazofurin) are C-nucleosides, and two of them (GS-6620, remdesivir) also contain a phosphoramidate part. The C-nucleoside and phosphoramidate (and for the adenine analogues the 1'-cyano group as well) may be considered as essential attributes for their antiviral activity.


Assuntos
Adenina/análogos & derivados , Antivirais/química , Guanina/análogos & derivados , Febres Hemorrágicas Virais/tratamento farmacológico , Adenina/farmacologia , Adenina/uso terapêutico , Amidas/química , Amidas/metabolismo , Amidas/farmacologia , Amidas/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , Pareamento de Bases , Ebolavirus/efeitos dos fármacos , Guanina/farmacologia , Guanina/uso terapêutico , Humanos , Nucleotídeos/química , Nucleotídeos/uso terapêutico , Ácidos Fosfóricos/química , Ácidos Fosfóricos/uso terapêutico , Pirazinas/química , Pirazinas/metabolismo , Pirazinas/farmacologia , Pirazinas/uso terapêutico , Triazinas/química , Triazinas/uso terapêutico
19.
PLoS Negl Trop Dis ; 13(8): e0007512, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31381606

RESUMO

BACKGROUND: As of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo. Since the beginning of October 2018, the outbreak has largely shifted into regions in which active armed conflict has occurred, and in which EVD cases and their contacts have been difficult for health workers to reach. We used available data on the current outbreak, with case-count time series from prior outbreaks, to project the short-term and long-term course of the outbreak. METHODS: For short- and long-term projections, we modeled Ebola virus transmission using a stochastic branching process that assumes gradually quenching transmission rates estimated from past EVD outbreaks, with outbreak trajectories conditioned on agreement with the course of the current outbreak, and with multiple levels of vaccination coverage. We used two regression models to estimate similar projection periods. Short- and long-term projections were estimated using negative binomial autoregression and Theil-Sen regression, respectively. We also used Gott's rule to estimate a baseline minimum-information projection. We then constructed an ensemble of forecasts to be compared and recorded for future evaluation against final outcomes. From August 20, 2018 to February 25, 2019, short-term model projections were validated against known case counts. RESULTS: During validation of short-term projections, from one week to four weeks, we found models consistently scored higher on shorter-term forecasts. Based on case counts as of February 25, the stochastic model projected a median case count of 933 cases by February 18 (95% prediction interval: 872-1054) and 955 cases by March 4 (95% prediction interval: 874-1105), while the auto-regression model projects median case counts of 889 (95% prediction interval: 876-933) and 898 (95% prediction interval: 877-983) cases for those dates, respectively. Projected median final counts range from 953 to 1,749. Although the outbreak is already larger than all past Ebola outbreaks other than the 2013-2016 outbreak of over 26,000 cases, our models do not project that it is likely to grow to that scale. The stochastic model estimates that vaccination coverage in this outbreak is lower than reported in its trial setting in Sierra Leone. CONCLUSIONS: Our projections are concentrated in a range up to about 300 cases beyond those already reported. While a catastrophic outbreak is not projected, it is not ruled out, and prevention and vigilance are warranted. Prospective validation of our models in real time allowed us to generate more accurate short-term forecasts, and this process may prove useful for future real-time short-term forecasting. We estimate that transmission rates are higher than would be seen under target levels of 62% coverage due to contact tracing and vaccination, and this model estimate may offer a surrogate indicator for the outbreak response challenges.


Assuntos
Ebolavirus/patogenicidade , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/prevenção & controle , Doença pelo Vírus Ebola/transmissão , Cobertura Vacinal , República Democrática do Congo/epidemiologia , Surtos de Doenças/prevenção & controle , Pessoal de Saúde , Humanos , Modelos Teóricos , Estudos Prospectivos , Análise de Regressão
20.
Emerg Microbes Infect ; 8(1): 1086-1097, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31339465

RESUMO

In the last few decades, Ebola virus (EBOV) has emerged periodically and infected people in Africa, resulting in an extremely high mortality rate. With no available prophylaxis or cure so far, a highly effective Ebola vaccine is urgently needed. In this study, we developed a novel chimpanzee adenovirus-based prime-boost vaccine by exploiting two recombinant replication-deficient chimpanzee adenoviral vectors, AdC7 and AdC68, which express glycoproteins (GP) of the EBOV strain identified in the 2014 outbreak. Our results indicated that a single immunization using AdC7 or AdC68 could stimulate potent EBOV-specific antibody responses, whereas the AdC7 prime-AdC68 boost regimen induced much stronger and sustained humoral and cellular immune responses in both mice and rhesus monkeys, compared with AdC7 or AdC68 single vaccination or the AdC68 prime-AdC7 boost regimen. This prime-boost vaccine could also protect mice from the simulated infection with EBOV-like particle (EBOVLP) in biosafety level 2 (BSL-2) laboratories, and antibodies from the prime-boost immunized rhesus macaques could passively provide protection against EBOVLP infection. Altogether, our results show that the AdC7 prime-AdC68 boost vaccine is a promising candidate for further development to combat EBOV infections.


Assuntos
Adenoviridae/imunologia , Ebolavirus/imunologia , Doença pelo Vírus Ebola/imunologia , Adenoviridae/genética , Animais , Anticorpos Antivirais/imunologia , Modelos Animais de Doenças , Ebolavirus/genética , Feminino , Vetores Genéticos/genética , Vetores Genéticos/imunologia , Doença pelo Vírus Ebola/prevenção & controle , Doença pelo Vírus Ebola/virologia , Humanos , Imunidade Celular , Imunização Secundária , Macaca mulatta , Masculino , Camundongos , Camundongos Endogâmicos BALB C
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