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 JovemRESUMO
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.
