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1.
Infect Dis Clin North Am ; 33(4): 933-951, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31668199

RESUMO

Lassa fever outbreaks West Africa have caused up to 10,000 deaths annually. Primary infection occurs from contact with Lassa virus-infected rodents and exposure to their excreta, blood, or meat. Incubation takes 2 to 21 days. Symptoms are difficult to distinguish from malaria, typhoid, dengue, yellow fever, and other viral hemorrhagic fevers. Clinical manifestations range from asymptomatic, to mild, to severe fulminant disease. Ribavirin can improve outcomes. Overall mortality is between 1% and 15%. Lassa fever should be considered in the differential diagnosis with travel to West Africa. There is an urgent need for rapid field-friendly diagnostics and preventive vaccine.


Assuntos
Febre Lassa/epidemiologia , África Ocidental/epidemiologia , Animais , Surtos de Doenças , Humanos , Febre Lassa/virologia , Murinae/virologia , Fatores de Risco , Zoonoses
2.
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
3.
Int J Infect Dis ; 89: 84-86, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31465848

RESUMO

BACKGROUND: The signs and symptoms of Lassa fever are initially indistinguishable from other febrile illnesses common in the tropics and complications of pregnancy. Surviving Lassa fever during pregnancy is rare. Only few cases have been documented. The antiviral drug of choice is ribavirin. CASE DESCRIPTION: A 25-year-old multigravida farmer with fever who was initially thought to have malaria in pregnancy at 29 weeks gestation. Further changes in her clinical state and laboratory tests led to a confirmation of Lassa fever. The Liver enzymes were markedly deranged and the packed cell volume was 27%. She commenced on ribavirin and subsequently was delivered of a live male neonate who was RT PCR negative for Lassa fever virus. Her clinical state improved, repeat RT PCR on day 15 was negative and she made full recovery. DISCUSSION: The case reported had similar clinical features of fever and abdominal pain and resulted in the initial diagnoses of Malaria in pregnancy. When she failed to respond to antimalarial and antibiotics treatments, a strong suspicion of viral hemorrhagic fever was made. At this time the patient was in advanced stage of the disease with bleeding from vagina and puncture sites. On the third day of admission she was delivered of a live male neonate who remained negative after 2 consecutive RT PCR tests for Lassa fever virus. Lassa fever carries a high risk of death to the fetus throughout pregnancy and to the mother in the third trimester. Mothers with Lassa fever improved rapidly after evacuation of the uterus by spontaneous abortion, or normal delivery. She was clinically stable following delivery. Her laboratory investigations were essentially normal. Throughout her management transmission based precautions were observed. None of the six close contacts developed symptoms after been followed up for 21 days. CONCLUSION: This report adds to the body of literature that individuals can survive Lassa fever during pregnancy with good maternal and fetal outcome.


Assuntos
Febre Lassa/virologia , Complicações na Gravidez/virologia , Adulto , Antivirais/uso terapêutico , Feminino , Febre/diagnóstico , Febre/tratamento farmacológico , Febre/fisiopatologia , Febre/virologia , Humanos , Recém-Nascido , Febre Lassa/diagnóstico , Febre Lassa/tratamento farmacológico , Febre Lassa/fisiopatologia , Vírus Lassa/efeitos dos fármacos , Vírus Lassa/genética , Vírus Lassa/isolamento & purificação , Masculino , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/fisiopatologia , Resultado da Gravidez , Ribavirina/uso terapêutico
4.
Cell ; 178(4): 1004-1015.e14, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398326

RESUMO

Lassa virus (LASV) causes hemorrhagic fever and is endemic in West Africa. Protective antibody responses primarily target the LASV surface glycoprotein (GPC), and GPC-B competition group antibodies often show potent neutralizing activity in humans. However, which features confer potent and broadly neutralizing antibody responses is unclear. Here, we compared three crystal structures of LASV GPC complexed with GPC-B antibodies of varying neutralization potency. Each GPC-B antibody recognized an overlapping epitope involved in binding of two adjacent GPC monomers and preserved the prefusion trimeric conformation. Differences among GPC-antibody interactions highlighted specific residues that enhance neutralization. Using structure-guided amino acid substitutions, we increased the neutralization potency and breadth of these antibodies to include all major LASV lineages. The ability to define antibody residues that allow potent and broad neutralizing activity, together with findings from analyses of inferred germline precursors, is critical to develop potent therapeutics and for vaccine design and assessment.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Células Germinativas/imunologia , Febre Lassa/imunologia , Vírus Lassa/imunologia , Glicoproteínas de Membrana/química , Proteínas do Envelope Viral/química , Animais , Antígenos Virais/imunologia , Chlorocebus aethiops , Drosophila/citologia , Epitopos/química , Epitopos/imunologia , Células HEK293 , Humanos , Febre Lassa/virologia , Glicoproteínas de Membrana/imunologia , Estrutura Secundária de Proteína , Células Vero , Proteínas do Envelope Viral/imunologia , Vacinas Virais/imunologia
5.
Emerg Infect Dis ; 25(9): 1753-1756, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31441759

RESUMO

Lassa fever has not been reported in Côte d'Ivoire. We performed a retrospective analysis of human serum samples collected in Côte d'Ivoire in the dry seasons (January-April) during 2015-2018. We identified a fatal human case of Lassa fever in the Bangolo District of western Côte d'Ivoire during 2015.


Assuntos
Febre Lassa/epidemiologia , Vírus Lassa/isolamento & purificação , Adulto , Animais , Costa do Marfim/epidemiologia , Reservatórios de Doenças , Feminino , Humanos , Febre Lassa/sangue , Febre Lassa/transmissão , Febre Lassa/virologia , Vírus Lassa/genética , Masculino , Estudos Retrospectivos , Roedores , Estudos Soroepidemiológicos
6.
Int J Infect Dis ; 87: 15-20, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31357056

RESUMO

OBJECTIVES: Lassa fever (LF) causes annual outbreaks in endemic regions with high mortality of symptomatic patients. Ribavirin is recommended as standard treatment for LF in national and international guidelines but the evidence base for this recommendation has been questioned recently. METHODS: We conducted a systematic review and included 6 studies providing efficacy data of ribavirin treatment for LF (PROSPERO protocol CRD42018103994). RESULTS: Besides retrospective case series, the evidence mostly relies on a single prospective clinical trial with critical risk of bias. In this trial, LF associated mortality is reduced for patients with elevated aspartate aminotransferase (AST) when treated with ribavirin (OR 0.41, 95% CI 0.23-0.73), while mortality is higher for patients without elevated AST (OR 2.37, 95% CI 1.07-5.25). CONCLUSIONS: Based on the available data, current treatment guidelines may therefore put patients with mild LF at increased risk of death. The role of ribavirin in the treatment of LF requires urgent reassessment.


Assuntos
Febre Lassa/tratamento farmacológico , Vírus Lassa/efeitos dos fármacos , Ribavirina/uso terapêutico , Aspartato Aminotransferases/metabolismo , Ensaios Clínicos como Assunto , Humanos , Febre Lassa/enzimologia , Febre Lassa/mortalidade , Febre Lassa/virologia , Vírus Lassa/fisiologia , Estudos Prospectivos , Estudos Retrospectivos
7.
Philos Trans R Soc Lond B Biol Sci ; 374(1775): 20180268, 2019 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-31056054

RESUMO

Lassa fever (LF) is a zoonotic disease that is widespread in West Africa and involves animal-to-human and human-to-human transmission. Animal-to-human transmission occurs upon exposure to rodent excreta and secretions, i.e. urine and saliva, and human-to-human transmission occurs via the bodily fluids of an infected person. To elucidate the seasonal drivers of LF epidemics, we employed a mathematical model to analyse the datasets of human infection, rodent population dynamics and climatological variations and capture the underlying transmission dynamics. The surveillance-based incidence data of human cases in Nigeria were explored, and moreover, a mathematical model was used for describing the transmission dynamics of LF in rodent populations. While quantifying the case fatality risk and the rate of exposure of humans to animals, we explicitly estimated the corresponding contact rate of humans with infected rodents, accounting for the seasonal population dynamics of rodents. Our findings reveal that seasonal migratory dynamics of rodents play a key role in regulating the cyclical pattern of LF epidemics. The estimated timing of high exposure of humans to animals coincides with the time shortly after the start of the dry season and can be associated with the breeding season of rodents in Nigeria. This article is part of the theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes'. This issue is linked with the subsequent theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control'.


Assuntos
Febre Lassa/epidemiologia , Febre Lassa/veterinária , Doenças dos Roedores/epidemiologia , Roedores/virologia , Animais , Humanos , Febre Lassa/transmissão , Febre Lassa/virologia , Vírus Lassa/fisiologia , Modelos Teóricos , Nigéria/epidemiologia , Doenças dos Roedores/transmissão , Doenças dos Roedores/virologia , Roedores/fisiologia , Estações do Ano , Zoonoses/epidemiologia , Zoonoses/transmissão , Zoonoses/virologia
8.
Emerg Infect Dis ; 25(6): 1066-1074, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31107222

RESUMO

Lassa fever (LF) is endemic to Nigeria, where the disease causes substantial rates of illness and death. In this article, we report an analysis of the epidemiologic and clinical aspects of the LF outbreak that occurred in Nigeria during January 1-May 6, 2018. A total of 1,893 cases were reported; 423 were laboratory-confirmed cases, among which 106 deaths were recorded (case-fatality rate 25.1%). Among all confirmed cases, 37 occurred in healthcare workers. The secondary attack rate among 5,001 contacts was 0.56%. Most (80.6%) confirmed cases were reported from 3 states (Edo, Ondo, and Ebonyi). Fatal outcomes were significantly associated with being elderly; no administration of ribavirin; and the presence of a cough, hemorrhaging, and unconsciousness. The findings in this study should lead to further LF research and provide guidance to those preparing to respond to future outbreaks.


Assuntos
Surtos de Doenças , Febre Lassa/diagnóstico , Febre Lassa/epidemiologia , Vírus Lassa , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Geografia Médica , História do Século XXI , Humanos , Lactente , Recém-Nascido , Febre Lassa/história , Febre Lassa/virologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Nigéria/epidemiologia , Razão de Chances , Prevalência , Vigilância em Saúde Pública , Estações do Ano , Avaliação de Sintomas , Adulto Jovem
9.
Antiviral Res ; 167: 68-77, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30953674

RESUMO

Lassa virus (LASV) causes Lassa hemorrhagic fever in humans and poses a significant threat to public health in West Africa. Current therapeutic treatments for Lassa fever are limited, making the development of novel countermeasures an urgent priority. In this study, we identified losmapimod, a p38 mitogen-activated protein kinase (MAPK) inhibitor, from 102 screened compounds as an inhibitor of LASV infection. Losmapimod exerted its inhibitory effect against LASV after p38 MAPK down-regulation, and, interestingly, had no effect on other arenaviruses capable of causing viral hemorrhagic fever. Mechanistic studies showed that losmapimod inhibited LASV entry by affecting the stable signal peptide (SSP)-GP2 subunit interface of the LASV glycoprotein, thereby blocking pH-dependent viral fusion. As an aryl heteroaryl bis-carboxyamide derivative, losmapimod represents a novel chemical scaffold with anti-LASV activity, and it provides a new lead structure for the future development of LASV fusion inhibitors.


Assuntos
Antivirais/farmacologia , Ciclopropanos/farmacologia , Vírus Lassa/efeitos dos fármacos , Piridinas/farmacologia , Internalização do Vírus/efeitos dos fármacos , Animais , Infecções por Arenaviridae/tratamento farmacológico , Arenavirus/efeitos dos fármacos , Linhagem Celular , Chlorocebus aethiops , Reposicionamento de Medicamentos , Inibidores Enzimáticos/farmacologia , Humanos , Febre Lassa/tratamento farmacológico , Febre Lassa/virologia , Células Vero , Proteínas Virais de Fusão/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
10.
J Mol Biol ; 431(11): 2095-2111, 2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-31004664

RESUMO

Lassa virus (LASV) is a notorious human pathogen in West Africa. Its class I trimeric spike complex displays a distinct architecture, and its cell entry mechanism involves unique attributes not shared by other related viruses. We determined the crystal structure of the GP2 fusion glycoprotein from the spike complex of LASV (GP2LASV) in its post-fusion conformation. GP2LASV adopts a canonical helical bundle configuration similarly to other viruses in its family. The core packing of GP2LASV, however, is more organized compared to GP2 from other viruses reducing the formation of internal hydrophobic cavities. We demonstrate a link between the formation of such unfavorable hydrophobic cavities and the efficiencies of membrane fusion and cell entry. Our study suggests that LASV has evolved a more efficient membrane fusogen compared to other viruses from its family by optimizing the post-fusion configuration of its GP2 module.


Assuntos
Febre Lassa/virologia , Vírus Lassa/fisiologia , Internalização do Vírus , Animais , Linhagem Celular , Cristalografia por Raios X , Células HEK293 , Humanos , Febre Lassa/metabolismo , Vírus Lassa/química , Fusão de Membrana , Simulação de Dinâmica Molecular , Conformação Proteica
11.
Emerg Infect Dis ; 25(5): 999-1002, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31002054

RESUMO

We report detection of Lassa virus and Crimean-Congo hemorrhagic fever virus infections in the area of Bamako, the capital of Mali. Our investigation found 2 cases of infection with each of these viruses. These results show the potential for both of these viruses to be endemic to Mali.


Assuntos
Vírus da Febre Hemorrágica da Crimeia-Congo , Febre Hemorrágica da Crimeia/epidemiologia , Febre Hemorrágica da Crimeia/virologia , Febre Lassa/epidemiologia , Febre Lassa/virologia , Vírus Lassa , Vírus da Febre Hemorrágica da Crimeia-Congo/classificação , Vírus da Febre Hemorrágica da Crimeia-Congo/genética , Humanos , Vírus Lassa/classificação , Vírus Lassa/genética , Mali/epidemiologia , Vigilância em Saúde Pública
12.
EBioMedicine ; 40: 605-613, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30711514

RESUMO

BACKGROUND: Lassa virus (LASV) is the etiologic agent of an acute hemorrhagic fever endemic in West Africa. Natural killer (NK) cells control viral infections in part through the interaction between killer cell immunoglobulin-like receptors (KIRs) and their ligands. LASV infection is associated with defective immune responses, including inhibition of NK cell activity in the presence of MHC-class 1+-infected target cells. METHODS: We compared individual KIR and HLA-class 1 genotypes of 68 healthy volunteers to 51 patients infected with LASV in Sierra Leone, including 37 survivors and 14 fatalities. Next, potential HLA-C1, HLA-C2, and HLA-Bw4 binding epitopes were in silico screened among LASV nucleoprotein (NP) and envelope glycoprotein (GP). Selected 10-mer peptides were then tested in peptide-HLA stabilization, KIR binding and polyfunction assays. FINDINGS: LASV-infected patients were similar to healthy controls, except for the inhibitory KIR2DL2 gene. We found a specific increase in the HLA-C1:KIR2DL2 interaction in fatalities (10/11) as compared to survivors (12/19) and controls (19/29). We also identified that strong of NP and GP viral epitopes was only observed with HLA-C molecules, and associated with strong inhibition of degranulation in the presence of KIR2DL+ NK cells. This inhibitory effect significantly increased in the presence of the vGP420 variant, detected in 28.1% of LASV sequences. INTERPRETATION: Our finding suggests that presentation of specific LASV epitopes by HLA-C alleles to the inhibitory KIR2DL2 receptor on NK cells could potentially prevent the killing of infected cells and provides insights into the mechanisms by which LASV can escape NK-cell-mediated immune pressure.


Assuntos
Epitopos/imunologia , Antígenos HLA-C/imunologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Febre Lassa/imunologia , Febre Lassa/metabolismo , Vírus Lassa/imunologia , Receptores KIR2DL2/metabolismo , Antígenos Virais/imunologia , Linhagem Celular , Citotoxicidade Imunológica , Mapeamento de Epitopos/métodos , Genótipo , Antígenos HLA-C/genética , Humanos , Tolerância Imunológica , Imunomodulação , Imunofenotipagem , Febre Lassa/genética , Febre Lassa/virologia , Ligação Proteica , Receptores KIR2DL2/genética
13.
Nat Biotechnol ; 37(2): 160-168, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30718881

RESUMO

Metagenomic sequencing has the potential to transform microbial detection and characterization, but new tools are needed to improve its sensitivity. Here we present CATCH, a computational method to enhance nucleic acid capture for enrichment of diverse microbial taxa. CATCH designs optimal probe sets, with a specified number of oligonucleotides, that achieve full coverage of, and scale well with, known sequence diversity. We focus on applying CATCH to capture viral genomes in complex metagenomic samples. We design, synthesize, and validate multiple probe sets, including one that targets the whole genomes of the 356 viral species known to infect humans. Capture with these probe sets enriches unique viral content on average 18-fold, allowing us to assemble genomes that could not be recovered without enrichment, and accurately preserves within-sample diversity. We also use these probe sets to recover genomes from the 2018 Lassa fever outbreak in Nigeria and to improve detection of uncharacterized viral infections in human and mosquito samples. The results demonstrate that CATCH enables more sensitive and cost-effective metagenomic sequencing.


Assuntos
Biologia Computacional/métodos , Genoma Viral , Metagenoma , Metagenômica , Animais , Culicidae/virologia , Surtos de Doenças , Biblioteca Gênica , Variação Genética , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Febre Lassa/virologia , Nigéria/epidemiologia , Sondas de Oligonucleotídeos , Oligonucleotídeos/genética , Análise de Sequência de DNA , Viroses
14.
Emerg Infect Dis ; 25(5): 1026-1027, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30807268

RESUMO

We reviewed data pertaining to the massive wave of Lassa fever cases that occurred in Nigeria in 2018. No new virus strains were detected, but in 2018, the outbreak response was intensified, additional diagnostic support was available, and surveillance sensitivity increased. These factors probably contributed to the high case count.


Assuntos
Surtos de Doenças , Febre Lassa/epidemiologia , Animais , História do Século XXI , Humanos , Incidência , Febre Lassa/diagnóstico , Febre Lassa/história , Febre Lassa/virologia , Vírus Lassa/classificação , Vírus Lassa/genética , Vírus Lassa/isolamento & purificação , Nigéria/epidemiologia , Vigilância em Saúde Pública , Estações do Ano
15.
Emerg Infect Dis ; 25(2): 245-248, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30666924

RESUMO

Lassa virus is a rodentborne arenavirus responsible for human cases of Lassa fever, a viral hemorrhagic fever, in West Africa and in travelers arriving to non-Lassa-endemic countries from West Africa. We describe a retrospective review performed through literature search of clinical and epidemiologic characteristics of all imported Lassa fever cases worldwide during 1969-2016. Our findings demonstrate that approximately half of imported cases had distinctive clinical features (defined as fever and >1 of the following: pharyngitis, sore throat, tonsillitis, conjunctivitis, oropharyngeal ulcers, or proteinuria). Delays in clinical suspicion of this diagnosis were common. In addition, no secondary transmission of Lassa fever to contacts of patients with low-risk exposures occurred, and infection of high-risk contacts was rare. Future public health investigations of such cases should focus on timely recognition of distinctive clinical features, earlier treatment of patients, and targeted public health responses focused on high-risk contacts.


Assuntos
Febre Lassa/epidemiologia , Doença Relacionada a Viagens , Viagem , Adolescente , Adulto , África Ocidental/epidemiologia , Idoso , História do Século XX , História do Século XXI , Humanos , Febre Lassa/história , Febre Lassa/transmissão , Febre Lassa/virologia , Pessoa de Meia-Idade , Vigilância em Saúde Pública , Fatores de Risco , Estações do Ano , Adulto Jovem
16.
Science ; 363(6422): 74-77, 2019 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-30606844

RESUMO

The 2018 Nigerian Lassa fever season saw the largest ever recorded upsurge of cases, raising concerns over the emergence of a strain with increased transmission rate. To understand the molecular epidemiology of this upsurge, we performed, for the first time at the epicenter of an unfolding outbreak, metagenomic nanopore sequencing directly from patient samples, an approach dictated by the highly variable genome of the target pathogen. Genomic data and phylogenetic reconstructions were communicated immediately to Nigerian authorities and the World Health Organization to inform the public health response. Real-time analysis of 36 genomes and subsequent confirmation using all 120 samples sequenced in the country of origin revealed extensive diversity and phylogenetic intermingling with strains from previous years, suggesting independent zoonotic transmission events and thus allaying concerns of an emergent strain or extensive human-to-human transmission.


Assuntos
Surtos de Doenças , Febre Lassa/virologia , Vírus Lassa/genética , Metagenômica/métodos , Epidemiologia Molecular , Animais , Genoma Viral , Humanos , Febre Lassa/transmissão , Nigéria/epidemiologia , Filogenia , Zoonoses/transmissão , Zoonoses/virologia
17.
J Infect Dis ; 219(11): 1818-1822, 2019 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-30517671

RESUMO

Lassa fever (LF) survivors develop various clinical manifestations including polyserositis, myalgia, epididymitis, and hearing loss weeks to months after recovery from acute infection. We demonstrate a systemic lymphoplasmacytic and histiocytic arteritis and periarteritis in guinea pigs more than 2 months after recovery from acute Lassa virus (LASV) infection. LASV was detected in the arterial tunica media smooth muscle cells by immunohistochemistry, in situ hybridization, and transmission electron microscopy. Our results suggest that the sequelae of LASV infection may be due to virus persistence resulting in systemic vascular damage. These findings shed light on the pathogenesis of LASV sequelae in convalescent human survivors.


Assuntos
Febre Lassa/virologia , Vírus Lassa/imunologia , Animais , Convalescença , Modelos Animais de Doenças , Progressão da Doença , Feminino , Cobaias , Humanos , Imuno-Histoquímica , Inflamação , Febre Lassa/patologia , Masculino
19.
PLoS Negl Trop Dis ; 12(11): e0006971, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30500827

RESUMO

Lassa virus (LASV) is endemic in parts of West Africa where it causes Lassa fever (LF), a viral hemorrhagic fever with frequent fatal outcomes. The diverse LASV strains are grouped into six major lineages based on the geographical location of the isolated strains. In this study, we have focused on the lineage II strains from southern Nigeria. We determined the viral sequences from positive cases of LF reported at tertiary hospitals in Ebonyi and Enugu between 2012 and 2016. Reverse transcription-polymerase chain reaction (RT-PCR) showed that 29 out of 123 suspected cases were positive for the virus among which 11 viral gene sequences were determined. Phylogenetic analysis of the complete coding sequences of the four viral proteins revealed that lineage II strains are broadly divided into two genetic clades that diverged from a common ancestor 195 years ago. One clade, consisting of strains from Ebonyi and Enugu, was more conserved than the other from Irrua, although the four viral proteins were evolving at similar rates in both clades. These results suggested that the viruses of these clades have been distinctively evolving in geographically separate parts of southern Nigeria. Furthermore, the epidemiological data of the 2014 outbreak highlighted the role of human-to-human transmission in this outbreak, which was supported by phylogenetic analysis showing that 13 of the 16 sequences clustered together. These results provide new insights into the evolution of LASV in southern Nigeria and have important implications for vaccine development, diagnostic assay design, and LF outbreak management.


Assuntos
Febre Lassa/virologia , Vírus Lassa/genética , Vírus Lassa/isolamento & purificação , Evolução Molecular , Variação Genética , Humanos , Febre Lassa/epidemiologia , Vírus Lassa/classificação , Nigéria/epidemiologia , Filogenia , Proteínas Virais/genética
20.
PLoS Negl Trop Dis ; 12(11): e0006829, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30399142

RESUMO

Lassa fever is a viral haemorrhagic fever caused by an arenavirus. The disease is endemic in West African countries, including Guinea. The rodents Mastomys natalensis and Mastomys erythroleucus have been identified as Lassa virus reservoirs in Guinea. In the absence of a vaccine, rodent control and human behavioural changes are the only options to prevent Lassa fever in highly endemic areas. We performed a 4 year intervention based on chemical rodent control, utilizing anticoagulant rodenticides in 3 villages and evaluating the rodent abundance before and after treatment. Three additional villages were investigated as controls. Analyses to assess the effectiveness of the intervention, bait consumption and rodent dynamics were performed. Anthropological investigations accompanied the intervention to integrate local understandings of human-rodent cohabitation and rodent control intervention. Patterns of bait consumption showed a peak at days 5-7 and no consumption at days 28-30. There was no difference between Bromadiolone and Difenacoum bait consumption. The main rodent species found in the houses was M. natalensis. The abundance of M. natalensis, as measured by the trapping success, varied between 3.6 and 16.7% before treatment and decreased significantly to 1-2% after treatment. Individuals in treated villages welcomed the intervention and trapping because mice are generally regarded as a nuisance. Immediate benefits from controlling rodents included protection of food and belongings. Before the intervention, local awareness of Lassa fever was non-existent. Despite their appreciation for the intervention, local individuals noted its limits and the need for complementary actions. Our results demonstrate that chemical treatment provides an effective tool to control local rodent populations and can serve as part of an effective, holistic approach combining rodent trapping, use of local rodenticides, environmental hygiene, house repairs and rodent-proof storage. These actions should be developed in collaboration with local stakeholders and communities.


Assuntos
Febre Lassa/transmissão , Murinae/fisiologia , Controle de Roedores/métodos , Rodenticidas/farmacologia , Animais , Reservatórios de Doenças/virologia , Guiné , Febre Lassa/epidemiologia , Febre Lassa/prevenção & controle , Febre Lassa/virologia , Vírus Lassa/fisiologia , Camundongos , Murinae/classificação , Murinae/virologia , Controle de Roedores/instrumentação , Saúde da População Rural
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