RESUMO
The H7N9 influenza virus causes a severe form of disease in humans. Neuraminidase inhibitors, including oral oseltamivir and injectable peramivir, are the first choices of antiviral treatment for such cases; however, the clinical efficacy of these drugs is questionable. Animal experimental models are essential for understanding the viral replication kinetics under the selective pressure of antiviral agents. This study demonstrates the antiviral activity of peramivir in a mouse model of H7N9 avian influenza virus infection. The data show that repeated administration of peramivir at 30 mg/kg of body weight successfully eradicated the virus from the respiratory tract and extrapulmonary tissues during the acute response, prevented clinical signs of the disease, including neuropathy, and eventually protected mice against lethal H7N9 influenza virus infection. Early treatment with peramivir was found to be associated with better disease outcomes.
Assuntos
Antivirais/farmacologia , Ciclopentanos/farmacologia , Inibidores Enzimáticos/farmacologia , Guanidinas/farmacologia , Subtipo H7N9 do Vírus da Influenza A/efeitos dos fármacos , Infecções por Orthomyxoviridae/tratamento farmacológico , Ácidos Carbocíclicos , Animais , Cães , Esquema de Medicação , Feminino , Humanos , Subtipo H7N9 do Vírus da Influenza A/enzimologia , Subtipo H7N9 do Vírus da Influenza A/crescimento & desenvolvimento , Injeções Intramusculares , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos C57BL , Neuraminidase/antagonistas & inibidores , Neuraminidase/metabolismo , Infecções por Orthomyxoviridae/mortalidade , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia , Oseltamivir/farmacologia , Análise de Sobrevida , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Proteínas Virais/antagonistas & inibidores , Proteínas Virais/metabolismo , Replicação Viral/efeitos dos fármacosRESUMO
BACKGROUND: Influenza H7N9 has become an endemic pathogen in China where circulating virus is found extensively in wild birds and domestic poultry. Two epidemic waves of Human H7N9 infections have taken place in Eastern and South Central China during the years of 2013 and 2014. In this study, we report on the first four human cases of influenza H7N9 in Shantou, Guangdong province, which occurred during the second H7N9 wave, and the subsequent analysis of the viral isolates. METHODS: Viral genomes were subjected to multisegment amplification and sequenced in an Illumina MiSeq. Later, phylogenetic analyses of influenza H7N9 viruses were performed to establish the evolutionary context of the disease in humans. RESULTS: The sequences of the isolates from Shantou have closer evolutionary proximity to the predominant Eastern H7N9 cluster (similar to A/Shanghai/1/2013 (H7N9)) than to the Southern H7N9 cluster (similar to A/Guangdong/1/2013 (H7N9)). CONCLUSIONS: Two distinct phylogenetic groups of influenza H7N9 circulate currently in China and cause infections in humans as a consequence of cross-species spillover from the avian disease. The Eastern cluster, which includes the four isolates from Shantou, presents a wide geographic distribution and overlaps with the more restricted area of circulation of the Southern cluster. Continued monitoring of the avian disease is of critical importance to better understand and predict the epidemiological behaviour of the human cases.
Assuntos
Genoma Viral/genética , Subtipo H7N9 do Vírus da Influenza A/genética , Influenza Humana/epidemiologia , RNA Viral/análise , China/epidemiologia , Variação Genética , Humanos , Subtipo H7N9 do Vírus da Influenza A/isolamento & purificação , Influenza Humana/virologia , FilogeniaAssuntos
Transmissão de Doença Infecciosa do Paciente para o Profissional , Subtipo H7N9 do Vírus da Influenza A/genética , Influenza Humana/transmissão , Adulto , China , Infecção Hospitalar , Hospitais Universitários , Humanos , Subtipo H7N9 do Vírus da Influenza A/isolamento & purificação , Influenza Humana/virologia , Masculino , Filogenia , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Southern China experienced few cases of H7N9 during the first wave of human infections in the spring of 2013. The second and now the third waves of H7N9 infections have been localized mostly in Southern China with the Guangdong province an epicenter for the generation of novel H7N9 reassortants. Clusters of human infections show human-to-human transmission to be a rare but well-documented event. A recent cluster of infections involving hospital health care workers stresses the importance of care givers utilizing personal protective equipment in treating H7N9 infected or suspected patients.