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1.
Biomed Environ Sci ; 32(5): 363-370, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31217053

RESUMO

OBJECTIVE: People in Western Africa suffer greatly from febrile jaundice, which is caused by a variety of pathogens. However, yellow fever virus (YFV) is the only pathogen under surveillance in Sierra Leone owing to the undeveloped medical and public health system there. Most of the results of YFV identification are negative. Elucidation of the pathogen spectrum is required to reduce the prevalence of febrile jaundice. METHODS: In the present study, we used Ion Torrent semiconductor sequencing to profile the pathogen spectrum in archived YFV-negative sera from 96 patients in Sierra Leone who presented with unexplained febrile jaundice. RESULTS: The most frequently identified sequencing reads belonged to the following pathogens: cytomegalovirus (89.58%), Epstein-Barr virus (55.21%), hepatitis C virus (34.38%), rhinovirus (28.13%), hepatitis A virus (20.83%), coxsackievirus (10.42%), Ebola virus (8.33%), hepatitis E virus (8.33%), lyssavirus (4.17%), leptospirosis (4.17%), chikungunya virus (2.08%), Crimean-Congo hemorrhagic fever virus (1.04%), and hepatitis B virus (1.04%). CONCLUSION: The distribution of sequencing reads suggests a broader spectrum of pathogens for consideration in clinical diagnostics and epidemiological surveillance in Sierra Leone.


Assuntos
Febre/virologia , Icterícia/virologia , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Febre/epidemiologia , Humanos , Icterícia/epidemiologia , Masculino , Análise de Sequência , Serra Leoa/epidemiologia , Adulto Jovem
2.
Infect Dis Poverty ; 8(1): 15, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30827277

RESUMO

BACKGROUND: The 2014-2016 Ebola virus epidemic in West Africa was the largest outbreak of Ebola virus disease (EVD) in history. Clarifying the influence of other prevalent diseases such as human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) will help improve treatment and supportive care of patients with EVD. CASE PRESENTATION: We examined HIV and hepatitis C virus (HCV) antibody prevalence among suspected EVD cases from the Sierra Leone-China Friendship Biological Safety Laboratory during the epidemic in Sierra Leone. HIV and HCV antibodies were tested in 678 EVD-negative samples by enzyme-linked immunosorbent assay. A high HIV prevalence (17.6%) and low HCV prevalence (0.22%) were observed among the suspected cases. Notably, we found decreased HIV positive rates among the suspected cases over the course of the epidemic. This suggests a potentially beneficial effect of an improved public health system after assistance from the World Health Organization and other international aid organizations. CONCLUSIONS: This EVD epidemic had a considerable impact on the public health system and influenced the prevalence of HIV found among suspected cases in Sierra Leone, but also provided an opportunity to establish a better surveillance network for infectious diseases.


Assuntos
Epidemias/estatística & dados numéricos , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Doença pelo Vírus Ebola/complicações , Doença pelo Vírus Ebola/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prevalência , Serra Leoa/epidemiologia , Adulto Jovem
3.
Clin Infect Dis ; 68(10): 1763-1768, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-30239602

RESUMO

During the late phase of the large West-African Ebola virus disease (EVD) outbreak, the majority of patients were cared for in designated treatment centers. However, the preexisting healthcare infrastructure was already overwhelmed by the outbreak. This had a huge impact on other, non-EVD-related diseases, causing an unprecedented increase in morbidity and mortality, which most likely exceeded the toll due to EVD directly. Consequently, a crucial question is how to provide appropriate healthcare and safeguard functionality of a healthcare system that also serves patients not suspected or diagnosed to have EVD. Here, we report on the Lion Heart Medical Center's experience in Sierra Leone and note that a case definition of Ebola that is broader than those commonly applied may be better suited when it is necessary to identify atypically presenting, pauci-symptomatic cases.

4.
SAHARA J ; 15(1): 138-145, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30257611

RESUMO

Evaluations of community-based antiretroviral therapy (ART) programmes have demonstrated positive outcomes, but little is known about the impact of tapering community-based ART. The objective of this study was to assess 24-month HIV retention outcomes of a community-based ART programme and its tapered visit frequency in Koidu City, Sierra Leone. This retrospective, quasi-experimental study compared outcomes of 52 HIV-infected persons initiated on community-based ART against 91 HIV-infected persons receiving the standard of care from November 2009 to February 2013. The community-based ART pilot programme was designed to strengthen the standard of care through a comprehensive, patient-centred case management strategy. The strategy included medical, educational, psychological, social, and economic support. Starting in October 2011, the frequency of home visits was tapered from twice daily every day per week to once daily three days per week. Outcomes were retention in care at 12 and 24 months and adherence to ART over a three-month time period. Participants who received community-based ART had significantly higher retention than those receiving standard of care. At 12 months, retention rates for community-based ART and standard of care were 61.5% and 31.9%, respectively (p < .01). At 24 months, retention rates for community-based ART and standard of care were 73.1% and 44.0%, respectively (p < .01). Significant differences in levels of adherence were observed when comparing community-based ART against persons receiving standard of care (p < .05). No differences in adherence levels were observed between groups of people receiving various frequencies of home visits. Our pilot programme in Koidu City provides new evidence that community-based ART has the potential to improve retention and adherence outcomes for HIV-infected persons, regardless of the frequency of home visits. Overcoming the barriers to HIV care requires a comprehensive, patient-centred approach that may include clinic-based and community-based interventions.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Serviços de Saúde Comunitária , Infecções por HIV/tratamento farmacológico , Visita Domiciliar/estatística & dados numéricos , Adesão à Medicação/estatística & dados numéricos , Adulto , Contagem de Linfócito CD4 , Terapia Diretamente Observada/estatística & dados numéricos , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , Serra Leoa/epidemiologia , Carga Viral
5.
Virol Sin ; 33(4): 323-334, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30066045

RESUMO

This study aimed to investigate the serological characteristics of Ebola virus (EBOV) infection during the late phase of the Ebola outbreak in Sierra Leone. In total, 877 blood samples from 694 suspected Ebola virus disease (EVD) cases assessed from March to December 2015, were analyzed via real-time reverse transcription polymerase chain reaction (RT-PCR) for viral RNA and enzyme-linked immunosorbent assay (ELISA) and Luminex to detect antibodies against EBOV. Viral load and EBOV-specific IgM/IgG titers displayed a declining trend during March to December 2015. Viral RNA load decreased rapidly at earlier stages after disease onset, while EBOV-specific IgM and IgG still persisted in 58.1% (18/31) and 93.5% (29/31) of the confirmed EVD patients and in 3.8% (25/663) and 17.8% (118/663) of the RNA-negative suspected patients in the later phase, respectively. Dynamic analysis of longitudinally collected samples from eight EVD patients revealed typically reversed trends of declining viral load and increasing IgM and/or IgG titers in response to the EBOV infection. The present results indicate that certain populations of Sierra Leone developed immunity to an EBOV infection in the late phase of the outbreak, providing novel insights into the risk assessment of EBOV infections among human populations.


Assuntos
Surtos de Doenças , Ebolavirus/genética , Ebolavirus/imunologia , Doença pelo Vírus Ebola/sangue , Doença pelo Vírus Ebola/epidemiologia , Anticorpos Antivirais/sangue , Ensaio de Imunoadsorção Enzimática , Doença pelo Vírus Ebola/virologia , Humanos , RNA Viral/sangue , Reação em Cadeia da Polimerase em Tempo Real , Serra Leoa/epidemiologia , Fatores de Tempo , Carga Viral
6.
J Infect Dis ; 217(suppl_1): S6-S15, 2018 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-29788345
7.
Infect Dis Rep ; 10(3): 7725, 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30631407

RESUMO

During the mid-transmission period of the Ebola virus disease (EVD) outbreak in Sierra Leone, a 19-year-old pregnant woman, who was a petty trader in a health facility in Freetown, noticing no fetal movement for the past 3 days, reported to a health facility. Medical history and laboratory testing showed no abnormalities except that she was positive for sickle cell. She was not known to any surveillance team of having any epidemiological link to EVD case. She was induced with oral medications as well as IV infusion. EVD test showed that the fetus was positive to EVD with a high threshold value of 21, while the woman was negative for EVD with a threshold value of 42. The woman was positive to EVD IgG but negative to EVD IgM by ELISA technique. This is a rare EVD case in the period of medium transmission. We conclude that the woman may have come into contact with a low dose of virus not enough to cause a full blown EVD and that her immune system was able to stop the virus from further replication.

8.
JCI Insight ; 2(15)2017 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-28768904

RESUMO

Sierra Leone was the most severely affected country in Western Africa during the 2013-2016 outbreak of Ebola virus disease (EVD). Previous genome surveillance studies have revealed the origin, diversity, and evolutionary dynamics of the Ebola virus (EBOV); however, the information regarding EBOV sequences is insufficient, especially the clinical outcomes, given that the correlation between the clinical outcomes and the genetic evolution of EBOV is still not clear. Here, we collected and curated a comprehensive data set that includes 514 EBOV genome sequences from patients with confirmed EVD (including 60 sequences not previously studied), >87.5% of which have residence information and definitive clinical outcomes. Phylogenetic reconstruction revealed 11 lineages of EBOV in Sierra Leone. The median-joining haplotype network showed that haplotypes that are associated with lethal outcomes tend to contribute more to the spread of the EBOV in Sierra Leone than those with live outcomes. Analyses of the spatial-temporal distribution unraveled the lineage-distinctive distribution patterns. Different viral lineages have different case fatality rates (CFRs) during the same stage of the outbreak, implying that several lineages featuring SNPs may correlate with increased/decreased CFRs. This study provides invaluable data sets of EBOV infection and highlights the potential SNPs for further in-depth investigation.

9.
PLoS Negl Trop Dis ; 11(6): e0005665, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28628619

RESUMO

BACKGROUND: In August 2014, the National Institute for Communicable Diseases (NICD) in South Africa established a modular high-biosafety field Ebola diagnostic laboratory (SA FEDL) near Freetown, Sierra Leone in response to the rapidly increasing number of Ebola virus disease (EVD) cases. METHODS AND FINDINGS: The SA FEDL operated in the Western Area of Sierra Leone, which remained a "hotspot" of the EVD epidemic for months. The FEDL was the only diagnostic capacity available to respond to the overwhelming demand for rapid EVD laboratory diagnosis for several weeks in the initial stages of the EVD crisis in the capital of Sierra Leone. Furthermore, the NICD set out to establish local capacity amongst Sierra Leonean nationals in all aspects of the FEDL functions from the outset. This led to the successful hand-over of the FEDL to the Sierra Leone Ministry of Health and Sanitation in March 2015. Between 25 August 2014 and 22 June 2016, the laboratory tested 11,250 specimens mostly from the Western Urban and Western Rural regions of Sierra Leone, of which 2,379 (21.14%) tested positive for Ebola virus RNA. CONCLUSIONS: The bio-safety standards and the portability of the SA FEDL, offered a cost-effective and practical alternative for the rapid deployment of a field-operated high biocontainment facility. The SA FEDL teams demonstrated that it is highly beneficial to train the national staff in the course of formidable disease outbreak and accomplished their full integration into all operational and diagnostic aspects of the laboratory. This initiative contributed to the international efforts in bringing the EVD outbreak under control in Sierra Leone, as well as capacitating local African scientists and technologists to respond to diagnostic needs that might be required in future outbreaks of highly contagious pathogens.


Assuntos
Contenção de Riscos Biológicos/métodos , Testes Diagnósticos de Rotina/métodos , Doença pelo Vírus Ebola/diagnóstico , Laboratórios/organização & administração , Doença pelo Vírus Ebola/epidemiologia , Humanos , Cooperação Internacional , Serra Leoa/epidemiologia , África do Sul
10.
PLoS Negl Trop Dis ; 11(5): e0005622, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28505171

RESUMO

BACKGROUND: Ebola virus emerged in West Africa in December 2013. The high population mobility and poor public health infrastructure in this region led to the development of the largest Ebola virus disease (EVD) outbreak to date. METHODOLOGY/PRINCIPAL FINDINGS: On September 26, 2014, China dispatched a Mobile Biosafety Level-3 Laboratory (MBSL-3 Lab) and a well-trained diagnostic team to Sierra Leone to assist in EVD diagnosis using quantitative real-time PCR, which allowed the diagnosis of suspected EVD cases in less than 4 hours from the time of sample receiving. This laboratory was composed of three container vehicles equipped with advanced ventilation system, communication system, electricity and gas supply system. We strictly applied multiple safety precautions to reduce exposure risks. Personnel, materials, water and air flow management were the key elements of the biosafety measures in the MBSL-3 Lab. Air samples were regularly collected from the MBSL-3 Lab, but no evidence of Ebola virus infectious aerosols was detected. Potentially contaminated objects were also tested by collecting swabs. On one occasion, a pipette tested positive for EVD. A total of 1,635 suspected EVD cases (824 positive [50.4%]) were tested from September 28 to November 11, 2014, and no member of the diagnostic team was infected with Ebola virus or other pathogens, including Lassa fever. The specimens tested included blood (69.2%) and oral swabs (30.8%) with positivity rates of 54.2% and 41.9%, respectively. The China mobile laboratory was thus instrumental in the EVD outbreak response by providing timely and reliable diagnostics. CONCLUSIONS/SIGNIFICANCE: The MBSL-3 Lab significantly contributed to establishing a suitable laboratory response capacity during the emergence of EVD in Sierra Leone.


Assuntos
Contenção de Riscos Biológicos , Arquitetura de Instituições de Saúde/normas , Doença pelo Vírus Ebola/diagnóstico , Laboratórios/normas , Segurança/normas , Ebolavirus , Epidemias , Doença pelo Vírus Ebola/epidemiologia , Humanos , Laboratórios/organização & administração , RNA Viral/análise , Serra Leoa/epidemiologia , Fluxo de Trabalho
11.
J Infect Dis ; 215(7): 1107-1110, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28498995

RESUMO

We performed Ebola virus disease diagnosis and viral load estimation for Ebola cases in Sierra Leone during the late stage of the 2014-2015 outbreak (January-March 2015) and analyzed antibody and cytokine levels and the viral genome sequences. Ebola virus disease was confirmed in 86 of 1001 (9.7%) patients, with an overall case fatality rate of 46.8%. Fatal cases exhibited significantly higher levels of viral loads, cytokines, and chemokines at late stages of infection versus early stage compared with survivors. The viruses converged in a new clade within sublineage 3.2.4, which had a significantly lower case fatality rate.


Assuntos
Ebolavirus/genética , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/imunologia , Carga Viral , Anticorpos Antivirais/sangue , Citocinas/sangue , Surtos de Doenças , Genoma Viral , Humanos , Serra Leoa/epidemiologia , Sobreviventes
12.
Front Public Health ; 5: 33, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28303239

RESUMO

INTRODUCTION: Western Area (WA) of Sierra Leone including the capital, Freetown, experienced an unprecedented outbreak of Ebola from 2014 to 2015. At the onset of the epidemic, there was little information about the epidemiology, transmission dynamics, and risk factors in urban settings as previous outbreaks were limited to rural/semi-rural settings. This study, therefore, aimed to describe the epidemiology of the outbreak and the factors which had most impact on the transmission of the epidemic and whether there were different drivers from those previously described in rural settings. METHODS: We conducted a descriptive epidemiology study in WA, Sierra Leone using secondary data from the National Ebola outbreak database. We also reviewed the Ebola situation reports, response strategy documents, and other useful documents. RESULTS: A total of 4,955 Ebola cases were identified between June 2014 and November 2015, although there were reports of cases occurring in WA toward end of May. All wards were affected, and Waterloo Area I (Ward 330), the capital city of Western Area Rural District, recorded the highest numbers of cases (580) and deaths (236). Majority of cases (63.4%) and deaths (66.8%) were in WA Urban District (WAU); 44 cases were imported from other provinces. Only 20% of cases had a history of contact with an Ebola case, and more than 30% were death alerts. Equal numbers of males and females were infected, and very few cases (3.2%) were health workers. Overall, transmission was through contact with infected individuals, and intense transmission occurred at the community level. In WAU, transmission was mostly between neighbors and among inhabitants of shared accommodations. The drivers of transmission included high population movement to and from WA, overcrowding, fear and lack of trust in the response, and negative community behaviors. Transmission was mostly through contact and with limited transmission through sex and breast milk. CONCLUSION: The unprecedented outbreak in WA was attributed to delayed detection, inadequate preparedness and response, intense population movements, overcrowding, and unresponsive communities. Anticipation, strengthening preparedness for early detection, and swift and effective response remains critical in mitigating a potential urban explosion of similar future outbreaks.

13.
J Public Health Afr ; 8(2): 732, 2017 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-29456826

RESUMO

A serosurvey of anti-Ebola Zaire virus nucleoprotein IgG prevalence was carried out among Ebola virus disease survivors and their Community Contacts in Bombali District, Sierra Leone. Our data suggest that the specie of Ebola virus (Zaire) responsible of the 2013-2016 epidemic in West Africa may cause mild or asymptomatic infection in a proportion of cases, possibly due to an efficient immune response.

14.
J Infect Dis ; 214(suppl 3): S258-S262, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27587631

RESUMO

During the Ebola virus outbreak of 2013-2016, the Viral Special Pathogens Branch field laboratory in Sierra Leone tested approximately 26 000 specimens between August 2014 and October 2015. Analysis of the B2M endogenous control Ct values showed its utility in monitoring specimen quality, comparing results with different specimen types, and interpretation of results. For live patients, blood is the most sensitive specimen type and oral swabs have little diagnostic utility. However, swabs are highly sensitive for diagnostic testing of corpses.


Assuntos
Surtos de Doenças , Ebolavirus/isolamento & purificação , Doença pelo Vírus Ebola/diagnóstico , RNA Viral/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Serviços de Laboratório Clínico , Ebolavirus/genética , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/virologia , Humanos , Laboratórios , Reação em Cadeia da Polimerase em Tempo Real/métodos , Sensibilidade e Especificidade , Serra Leoa/epidemiologia
15.
J Infect Dis ; 214(suppl 3): S210-S217, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27587634

RESUMO

BACKGROUND: Ebola virus disease (EVD) is a severe viral illness caused by Ebola virus (EBOV). The 2013-2016 EVD outbreak in West Africa is the largest recorded, with >11 000 deaths. Development of the ReEBOV Antigen Rapid Test (ReEBOV RDT) was expedited to provide a point-of-care test for suspected EVD cases. METHODS: Recombinant EBOV viral protein 40 antigen was used to derive polyclonal antibodies for RDT and enzyme-linked immunosorbent assay development. ReEBOV RDT limits of detection (LOD), specificity, and interference were analytically validated on the basis of Food and Drug Administration (FDA) guidance. RESULTS: The ReEBOV RDT specificity estimate was 95% for donor serum panels and 97% for donor whole-blood specimens. The RDT demonstrated sensitivity to 3 species of Ebolavirus (Zaire ebolavirus, Sudan ebolavirus, and Bundibugyo ebolavirus) associated with human disease, with no cross-reactivity by pathogens associated with non-EBOV febrile illness, including malaria parasites. Interference testing exhibited no reactivity by medications in common use. The LOD for antigen was 4.7 ng/test in serum and 9.4 ng/test in whole blood. Quantitative reverse transcription-polymerase chain reaction testing of nonhuman primate samples determined the range to be equivalent to 3.0 × 105-9.0 × 108 genomes/mL. CONCLUSIONS: The analytical validation presented here contributed to the ReEBOV RDT being the first antigen-based assay to receive FDA and World Health Organization emergency use authorization for this EVD outbreak, in February 2015.


Assuntos
Antígenos Virais/sangue , Surtos de Doenças , Ebolavirus/imunologia , Doença pelo Vírus Ebola/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Proteínas da Matriz Viral/sangue , África Ocidental/epidemiologia , Animais , Ebolavirus/isolamento & purificação , Ensaio de Imunoadsorção Enzimática , Doença pelo Vírus Ebola/virologia , Humanos , Imunoensaio , Limite de Detecção , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade
16.
J Infect Dis ; 214(suppl 3): S203-S209, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27521365

RESUMO

BACKGROUND: The 2013-2016 West African Ebola virus disease (EVD) epidemic is the largest recorded. Triage on the basis of clinical signs had limited success, and the time to diagnosis by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) could exceed 5 days. Here we describe the development and field validation of the ReEBOV Antigen Rapid Test (ReEBOV RDT) to aid triage of individuals with suspected EVD. METHODS: Samples from patients with suspected EVD were submitted to Kenema Government Hospital, Sierra Leone, for Lassa fever and EVD screening throughout 2014. Banked residual clinical samples were tested in November 2014 and January 2015 in a blinded field trial to estimate the clinical effectiveness of the ReEBOV RDT, compared with EBOV-specific qRT-PCR. RESULTS: Preliminary ReEBOV RDT performance demonstrated a positive percentage agreement (PPA) of 91.1% (195 of 214 results; 95% confidence interval [CI], 86.5%-94.6%) and a negative percentage agreement (NPA) of 90.2% (175 of 194; 95% CI, 85.1%-94.0%). The final estimates used by the Food and Drug Administration to determine whether to grant emergency use authorization for the test, which excluded a qRT-PCR reference method threshold cutoff, were a PPA of 62.1% (72 of 116 results; 95% CI, 52.6%-70.9%) and a NPA of 96.7% (58 of 60; 95% CI, 88.5%-99.6%), with a diagnostic likelihood of 18.6. A subsequent, independent evaluation by the World Health Organization generated results consistent with the preliminary performance estimates. CONCLUSIONS: The ReEBOV RDT demonstrated the potential to provide clinically effective rapid and accurate point-of-care test results and, thus, to be a powerful tool for increasing triage efficiency.


Assuntos
Antígenos Virais/sangue , Ebolavirus/imunologia , Doença pelo Vírus Ebola/diagnóstico , Imunoensaio/métodos , Sistemas Automatizados de Assistência Junto ao Leito , Ebolavirus/genética , Ebolavirus/isolamento & purificação , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/virologia , Hospitais , Humanos , RNA Viral/sangue , Kit de Reagentes para Diagnóstico , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Serra Leoa
17.
Clin Infect Dis ; 63(10): 1288-1294, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27553371

RESUMO

BACKGROUND: During 2014-2015, an outbreak of Ebola virus disease (EVD) swept across parts of West Africa. No approved antiviral drugs are available for Ebola treatment currently. METHODS: A retrospective clinical case series was performed for EVD patients in Sierra Leone-China Friendship Hospital. Patients with confirmed EVD were sequentially enrolled and treated with either World Health Organization (WHO)-recommended supportive therapy (control group) from 10 to 30 October, or treated with WHO-recommended therapy plus favipiravir (T-705) from 1 to 10 November 2014. Survival and virological characteristics were observed for 85 patients in the control group and 39 in the T-705 treatment group. RESULTS: The overall survival rate in the T-705 treatment group was higher than that of the control group (56.4% [22/39] vs 35.3% [30/85]; P = .027). Among the 35 patients who finished all designed endpoint observations, the survival rate in the T-705 treatment group (64.8% [11/17]) was higher than that of the control group (27.8% [5/18]). Furthermore, the average survival time of the treatment group (46.9 ± 5.6 days) was longer than that of the control group (28.9 ± 4.7 days). Most symptoms of patients in the treatment group improved significantly. Additionally, 52.9% of patients who received T-705 had a >100-fold viral load reduction, compared with only 16.7% of patients in the control group. CONCLUSIONS: Treatment of EVD with T-705 was associated with prolonged survival and markedly reduced viral load, which makes a compelling case for further randomized controlled trials of T-705 for treating EVD.


Assuntos
Amidas/uso terapêutico , Antivirais/uso terapêutico , Ebolavirus , Doença pelo Vírus Ebola/tratamento farmacológico , Doença pelo Vírus Ebola/mortalidade , Pirazinas/uso terapêutico , Adolescente , Adulto , Feminino , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/virologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Estudos Retrospectivos , Serra Leoa/epidemiologia , Carga Viral , Adulto Jovem
18.
J Infect Dis ; 214(suppl 3): S110-S121, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27402779

RESUMO

BACKGROUND: Kenema Government Hospital (KGH) has developed an advanced clinical and laboratory research capacity to manage the threat of Lassa fever, a viral hemorrhagic fever (VHF). The 2013-2016 Ebola virus (EBOV) disease (EVD) outbreak is the first to have occurred in an area close to a facility with established clinical and laboratory capacity for study of VHFs. METHODS: Because of its proximity to the epicenter of the EVD outbreak, which began in Guinea in March 2014, the KGH Lassa fever Team mobilized to establish EBOV surveillance and diagnostic capabilities. RESULTS: Augustine Goba, director of the KGH Lassa laboratory, diagnosed the first documented case of EVD in Sierra Leone, on 25 May 2014. Thereafter, KGH received and cared for numbers of patients with EVD that quickly overwhelmed the capacity for safe management. Numerous healthcare workers contracted and lost their lives to EVD. The vast majority of subsequent EVD cases in West Africa can be traced back to a single transmission chain that includes this first diagnosed case. CONCLUSIONS: Responding to the challenges of confronting 2 hemorrhagic fever viruses will require continued investments in the development of countermeasures (vaccines, therapeutic agents, and diagnostic assays), infrastructure, and human resources.


Assuntos
Surtos de Doenças , Ebolavirus/isolamento & purificação , Genoma Viral/genética , Doença pelo Vírus Ebola/epidemiologia , Febre Lassa/epidemiologia , Vírus Lassa/isolamento & purificação , Adolescente , Adulto , África Ocidental/epidemiologia , Criança , Pré-Escolar , Ebolavirus/genética , Monitoramento Epidemiológico , Feminino , Genômica , Guiné/epidemiologia , Doença pelo Vírus Ebola/diagnóstico , Doença pelo Vírus Ebola/transmissão , Doença pelo Vírus Ebola/virologia , Humanos , Febre Lassa/diagnóstico , Febre Lassa/transmissão , Febre Lassa/virologia , Vírus Lassa/genética , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA , Serra Leoa/epidemiologia , Adulto Jovem
19.
Nat Commun ; 7: 11544, 2016 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-27161536

RESUMO

Lassa fever is a severe multisystem disease that often has haemorrhagic manifestations. The epitopes of the Lassa virus (LASV) surface glycoproteins recognized by naturally infected human hosts have not been identified or characterized. Here we have cloned 113 human monoclonal antibodies (mAbs) specific for LASV glycoproteins from memory B cells of Lassa fever survivors from West Africa. One-half bind the GP2 fusion subunit, one-fourth recognize the GP1 receptor-binding subunit and the remaining fourth are specific for the assembled glycoprotein complex, requiring both GP1 and GP2 subunits for recognition. Notably, of the 16 mAbs that neutralize LASV, 13 require the assembled glycoprotein complex for binding, while the remaining 3 require GP1 only. Compared with non-neutralizing mAbs, neutralizing mAbs have higher binding affinities and greater divergence from germline progenitors. Some mAbs potently neutralize all four LASV lineages. These insights from LASV human mAb characterization will guide strategies for immunotherapeutic development and vaccine design.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Vírus Lassa/imunologia , Especificidade de Anticorpos , Antígenos Virais/química , Antígenos Virais/genética , Antígenos Virais/imunologia , Arenavirus/imunologia , Reações Cruzadas , Mapeamento de Epitopos , Epitopos/química , Epitopos/genética , Epitopos/imunologia , Humanos , Febre Lassa/imunologia , Febre Lassa/prevenção & controle , Vírus Lassa/genética , Modelos Moleculares , Mutagênese Sítio-Dirigida , Deleção de Sequência , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia
20.
Proc Natl Acad Sci U S A ; 113(16): 4488-93, 2016 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-27035948

RESUMO

Sierra Leone is the most severely affected country by an unprecedented outbreak of Ebola virus disease (EVD) in West Africa. Although successfully contained, the transmission dynamics of EVD and the impact of interventions in the country remain unclear. We established a database of confirmed and suspected EVD cases from May 2014 to September 2015 in Sierra Leone and mapped the spatiotemporal distribution of cases at the chiefdom level. A Poisson transmission model revealed that the transmissibility at the chiefdom level, estimated as the average number of secondary infections caused by a patient per week, was reduced by 43% [95% confidence interval (CI): 30%, 52%] after October 2014, when the strategic plan of the United Nations Mission for Emergency Ebola Response was initiated, and by 65% (95% CI: 57%, 71%) after the end of December 2014, when 100% case isolation and safe burials were essentially achieved, both compared with before October 2014. Population density, proximity to Ebola treatment centers, cropland coverage, and atmospheric temperature were associated with EVD transmission. The household secondary attack rate (SAR) was estimated to be 0.059 (95% CI: 0.050, 0.070) for the overall outbreak. The household SAR was reduced by 82%, from 0.093 to 0.017, after the nationwide campaign to achieve 100% case isolation and safe burials had been conducted. This study provides a complete overview of the transmission dynamics of the 2014-2015 EVD outbreak in Sierra Leone at both chiefdom and household levels. The interventions implemented in Sierra Leone seem effective in containing the epidemic, particularly in interrupting household transmission.


Assuntos
Bases de Dados Factuais , Ebolavirus , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/terapia , Doença pelo Vírus Ebola/transmissão , Modelos Biológicos , Feminino , Humanos , Masculino , Serra Leoa/epidemiologia
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