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1.
Vet Microbiol ; 239: 108477, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31767089

RESUMO

Swine influenza A viruses (swIAVs) cause acute respiratory syndromes in pigs and may also infect humans. Following the 2009 pandemic, a network was established in France to reinforce swIAV monitoring. This study reports virological and epidemiological data accumulated through passive surveillance conducted during 1,825 herd visits from 2011 to 2018. Among them, 887 (48.6 %) tested swIAV-positive. The proportion of positive cases remained stable year-on-year and year-round. The European avian-like swine H1N1 (H1avN1) virus was the most frequently identified (69.6 %), and was widespread across the country. The European human-like reassortant swine H1N2 (H1huN2) virus accounted for 22.1 % and was only identified in the north-western quarter and recently in the far north. The 2009 pandemic H1N1 (H1N1pdm) virus (3.6 %) was detected throughout the country, without settling in areas of higher pig densities. Its proportion increased in winter, during the seasonal epidemics in humans. The European human-like reassortant swine H3N2 as well as H1avN2 viruses were identified sporadically. In up to 30 % of swIAV-positive cases, pigs exhibited clinical signs of high intensity, regardless of the viral subtype and vaccination program. The recurrent pattern of the disease, i.e., an endemic infection at the herd level, was reported in 41% of cases and mainly affected post-weaning piglets (OR = 5.11 [3.36-7.76]). Interestingly, the study also revealed a significant association between the recurrent pattern and sow vaccination (OR = 1.96 [1.37-2.80]). Although restricted to the studied pig population, these results bring new knowledge about swIAV dynamics and infection patterns in pig herds in France.


Assuntos
Vírus da Influenza A , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/virologia , Animais , França/epidemiologia , Humanos , Vírus da Influenza A/classificação , Vírus da Influenza A/fisiologia , Vigilância da População , Prevalência , Zoonoses/epidemiologia , Zoonoses/virologia
2.
Zoonoses Public Health ; 66(7): 874-878, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31493311

RESUMO

We estimated that more than 11,000 people were exposed to highly pathogenic avian influenza viruses in EU/EEA countries over the outbreak period October 2016-September 2018 by cross-linking data submitted by Member States to European Food Safety Authority and EMPRES-i. A stronger framework for collecting human exposure data is required.


Assuntos
Influenza Aviária/virologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Animais , Animais Selvagens/virologia , Aves/virologia , União Europeia , Humanos , Vírus da Influenza A/classificação , Vírus da Influenza A/patogenicidade , Influenza Aviária/epidemiologia
3.
Int J Infect Dis ; 88: 113-119, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31401200

RESUMO

Here we review evidence for influenza A viruses (IAVs) moving from swine, avian, feline, equine, and canine species to infect humans. We review case reports, sero-epidemiological, archeo-epidemiological, environmental, and historical studies and consider trends in livestock farming. Although this focused review is not systematic, the aggregated data point to industrialized swine farming as the most likely source of future pandemic viruses, yet IAV surveillance on such farms is remarkably sparse. We recommend increased biosafety and biosecurity training for farm administrators and swine workers with One Health-oriented virus surveillance throughout industrialized farming and meat production lines. Collaborative partnerships with human medical researchers could aid in efforts to mitigate emerging virus threats by offering new surveillance and diagnostic technologies to livestock farming industries.


Assuntos
Vírus da Influenza A/fisiologia , Influenza Humana/virologia , Infecções por Orthomyxoviridae/veterinária , Animais , Aves , Gatos , Cães , Cavalos , Humanos , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Influenza Humana/transmissão , Infecções por Orthomyxoviridae/transmissão , Infecções por Orthomyxoviridae/virologia , Suínos
4.
Transbound Emerg Dis ; 66(6): 2411-2425, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31328387

RESUMO

Since 2014, H5 highly pathogenic avian influenza viruses (HPAIVs) from clade 2.3.4.4 have been persistently circulating in Southern China. This has caused huge losses in the poultry industry. In this study, we analysed the genetic characteristics of seven H5N6 HPAIVs of clade 2.3.4.4 that infected birds in Southern China in 2016. Phylogenetic analysis grouped the HA, PB2, PA, M and NS genes as MIX-like, and the NA genes grouped into the Eurasian lineage. The PB1 genes of the GS24, GS25, CK46 and GS74 strains belonged to the VN 2014-like group and the others were grouped as MIX-like. The NP genes of GS24 and GS25 strains belonged to the ZJ-like group, but the others were MIX-like. Thus, these viruses came from different genotypes, and the GS24, GS25, CK46 and GS74 strains displayed genotype recombination. Additionally, our results showed that the mean death time of all chickens inoculated with 105 EID50 of CK46 or GS74 viruses was 3 and 3.38 days, respectively. The viruses replicated at high titers in all tested tissues of the inoculated chickens. They also replicated in all tested tissues of naive contact chickens, but their replication titers in some tissues were significantly different (p < 0.05). Thus, the viruses displayed high pathogenicity and variable transmission in chickens. Therefore, it is necessary to focus on the pathogenic variation and molecular evolution of H5N6 HPAIVs in order to prevent and control avian influenza in China.


Assuntos
Vírus da Influenza A/genética , Vírus da Influenza A/patogenicidade , Influenza Aviária/transmissão , Animais , Galinhas/virologia , China , Evolução Molecular , Genótipo , Vírus da Influenza A/classificação , Filogenia , Recombinação Genética , Replicação Viral
5.
PLoS One ; 14(6): e0218506, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31242207

RESUMO

Genetically related highly pathogenic avian influenza viruses (HPAIVs) of H5N6 subtype caused outbreaks simultaneously in East Asia and Europe-geographically distinct regions-during winter 2017-2018. This situation prompted us to consider whether the application of phylogeographic analysis to a particular gene segment of AIVs could provide clues for understanding how AIV had been disseminated across the continent. Here, the N6 NA genes of influenza viruses isolated across the world were subjected to phylogeographic analysis to illustrate the inter- and intracontinental dissemination of AIVs. Those isolated in East Asia during winter and in Mongolia/Siberia during summer were comingled within particular clades of the phylogeographic tree. For AIVs in one clade, their dissemination in eastern Eurasia extended from Yakutia, Russia, in the north to East Asia in the south. AIVs in western Asia, Europe, and Mongolia were also comingled within other clades, indicating that Mongolia/Siberia plays an important role in the dissemination of AIVs across the Eurasian continent. Mongolia/Siberia may therefore have played a role in the simultaneous outbreaks of H5N6 HPAIVs in Europe and East Asia during the winter of 2017-2018. In addition to the long-distance intracontinental disseminations described above, intercontinental disseminations of AIVs between Eurasia and Africa and between Eurasia and North America were also observed. Integrating these results and known migration flyways suggested that the migration of wild birds and the overlap of flyways, such as that observed in Mongolia/Siberia and along the Alaskan Peninsula, contributed to the long-distance intra- and intercontinental dissemination of AIVs. These findings highlight the importance of understanding the movement of migratory birds and the dynamics of AIVs in breeding areas-especially where several migration flyways overlap-in forecasting outbreaks caused by HPAIVs.


Assuntos
Migração Animal , Animais Selvagens/virologia , Aves/virologia , Vírus da Influenza A/isolamento & purificação , Animais , Animais Selvagens/classificação , Ásia/epidemiologia , Aves/classificação , Surtos de Doenças/veterinária , Reservatórios de Doenças/virologia , Europa (Continente)/epidemiologia , Voo Animal , Genes Virais , Interações entre Hospedeiro e Microrganismos/genética , Especificidade de Hospedeiro/genética , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Influenza Aviária/epidemiologia , Influenza Aviária/virologia , América do Norte/epidemiologia , Filogenia , Filogeografia
6.
Int J Mol Sci ; 20(11)2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31151205

RESUMO

This study aimed at assessing the frequency and the distribution of influenza virus types/subtypes in 172 laboratory-confirmed influenza-positive patients admitted to intensive care units (ICUs) during the 2017-2018 season in the Lombardy region (Northern Italy), and to investigate the presence of molecular pathogenicity markers. A total of 102/172 (59.3%) patients had influenza A infections (83 A/H1N1pdm09, 2 H3N2 and 17 were untyped), while the remaining 70/172 (40.7%) patients had influenza B infections. The 222G/N mutation in the hemagglutinin gene was identified in 33.3% (3/9) of A/H1N1pdm09 strains detected in the lower respiratory tract (LRT) samples and was also associated with more severe infections, whereas no peculiar mutations were observed for influenza B strains. A single-point evolution was observed in site 222 of A/H1N1pdm09 viruses, which might advantage viral evolution by favouring virus binding and replication in the lungs. Data from 17 paired upper respiratory tract (URT) and LRT samples showed that viral load in LRT samples was mostly higher than that detected in URT samples. Of note, influenza viruses were undetectable in 35% of paired URT samples. In conclusion, LRT samples appear to provide more accurate clinical information than URT samples, thus ensuring correct diagnosis and appropriate treatment of patients with severe respiratory infections requiring ICU admission.


Assuntos
Cuidados Críticos , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Influenza Humana/epidemiologia , Influenza Humana/virologia , Unidades de Terapia Intensiva , Admissão do Paciente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Cuidados Críticos/métodos , Cuidados Críticos/estatística & dados numéricos , Feminino , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , História do Século XXI , Humanos , Lactente , Recém-Nascido , Influenza Humana/história , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Filogenia , Vigilância em Saúde Pública , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/história , Infecções Respiratórias/virologia , Estações do Ano , Carga Viral , Adulto Jovem
7.
Virology ; 534: 36-44, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31176062

RESUMO

Bangladesh has reported repeated outbreaks of highly pathogenic avian influenza (HPAI) A(H5) viruses in poultry since 2007. Because of the large number of live poultry markets (LPM) relative to the population density of poultry throughout the country, these markets can serve as sentinel sites for HPAI A(H5) detection. Through active LPM surveillance during June 2016-June 2017, HPAI A(H5N6) viruses along with 14 other subtypes of influenza A viruses were detected. The HPAI A(H5N6) viruses belonged to clade 2.3.4.4 and were likely introduced into Bangladesh around March 2016. Human infections with influenza clade 2.3.4.4 viruses in Bangladesh have not been identified, but the viruses had several molecular markers associated with potential human infection. Vigilant surveillance at the animal-human interface is essential to identify emerging avian influenza viruses with the potential to threaten public and animal health.


Assuntos
Vírus da Influenza A/isolamento & purificação , Influenza Aviária/virologia , Doenças das Aves Domésticas/virologia , Animais , Bangladesh/epidemiologia , Surtos de Doenças , Patos , Evolução Molecular , Gansos/virologia , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Influenza Aviária/epidemiologia , Filogenia , Doenças das Aves Domésticas/epidemiologia
8.
Virology ; 533: 1-11, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31071540

RESUMO

An H5N6 highly pathogenic avian influenza virus (HPAIV) outbreak occurred in poultry in Japan during January 2018, and H5N6 HPAIVs killed several wild birds in 3 prefectures during Winter 2017-2018. Time-measured phylogenetic analyses demonstrated that the Hemagglutinin (HA) and internal genes of these isolates were genetically similar to clade 2.3.4.4.B H5N8 HPAIVs in Europe during Winter 2016-2017, and Neuraminidase (NA) genes of the poultry and wild bird isolates were gained through distinct reassortments with AIVs that were estimated to have circulated possibly in Siberia during Summer 2017 and Summer 2016, respectively. Lethal infectious dose to chickens was similar between the poultry and wild-bird isolates. H5N6 HPAIVs during Winter 2017-2018 in Japan had higher 50% chicken lethal doses and lower transmission efficiency than the H5Nx HPAIVs that caused previous outbreaks in Japan, thus explaining in part why cases during the 2017-2018 outbreak were sporadic.


Assuntos
Animais Selvagens/virologia , Aves/virologia , Vírus da Influenza A/isolamento & purificação , Influenza Aviária/virologia , Doenças das Aves Domésticas/virologia , Adesinas de Escherichia coli/genética , Animais , Galinhas , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Influenza Aviária/epidemiologia , Influenza Aviária/transmissão , Japão/epidemiologia , Filogenia
9.
Transbound Emerg Dis ; 66(5): 1958-1970, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31077545

RESUMO

Emperor geese (Anser canagicus) are endemic to coastal areas within Beringia and have previously been found to have antibodies to or to be infected with influenza A viruses (IAVs) in Alaska. In this study, we use virological, serological and tracking data to further elucidate the role of emperor geese in the ecology of IAVs in Beringia during the non-breeding period. Specifically, we assess evidence for: (a) active IAV infection during spring staging, autumn staging and wintering periods; (b) infection with novel Eurasian-origin or interhemispheric reassortant viruses; (c) contemporary movement of geese between East Asia and North America; (d) previous exposure to viruses of 14 haemagglutinin subtypes, including Eurasian lineage highly pathogenic (HP) H5 IAVs; and (e) subtype-specific antibody seroconversion and seroreversion. Emperor geese were found to shed IAVs, including interhemispheric reassortant viruses, throughout the non-breeding period; migrate between Alaska and the Russian Far East prior to and following remigial moult; have antibodies reactive to a diversity of IAVs including, in a few instances, Eurasian lineage HP H5 IAVs; and exhibit relatively broad and stable patterns of population immunity among breeding females. Results of this study suggest that emperor geese may play an important role in the maintenance and dispersal of IAVs within Beringia during the non-breeding period and provide information that may be used to further optimize surveillance activities focused on the early detection of Eurasian-origin IAVs in North America.


Assuntos
Doenças das Aves/epidemiologia , Gansos , Vírus da Influenza A/fisiologia , Influenza Aviária/epidemiologia , Alaska/epidemiologia , Animais , Animais Selvagens , Doenças das Aves/virologia , Feminino , Vírus da Influenza A/classificação , Influenza Aviária/virologia , Prevalência , Federação Russa/epidemiologia , Estações do Ano
11.
PLoS One ; 14(3): e0213290, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30849093

RESUMO

Frequent typing and molecular characterization of influenza A (IAV) strains are crucial for the identification of circulating subtypes and for the selection of the subtypes' lineages to be included in the annually prepared vaccine cocktail. We investigated IAV sampled from an underrepresented population from Palestine. 200 nasopharyngeal aspirates (NPA) were collected between February and May of 2015 from Palestinians in East Jerusalem and the West Bank suffering from mild to severe symptoms of upper respiratory infections. NPA were screened for the presence of IAV using RT-PCR. Epidemiological data, hemagglutinin (HA) and neuraminidase (NA) gene sequences were analyzed in IAV positive samples. 50 samples tested positive for IAV; 48% of which were identified as A(H1N1)pdm09 and 52% as A(H3N2), respectively. Infection with A(H1N1)pdm09 occurred mainly in April, while A(H3N2) infections were mainly detected in March. Most IAV infections in 6-year-olds and below were attributed to subtype A(H3N2), while A(H1N1)pdm09 was responsible for most infections in adults above 18-year-olds. Analyses of HA and NA amino acid sequences revealed numerous substitutions. Thereafter, and based on the HA analysis, the Palestinian A(H1N1)pdm09 isolates fell into clade 6B, while the A(H3N2) isolates fell into clades 3C.2 and 3C.3, respectively. This study is significant in providing the first insight into the epidemiology and genetic properties of IAV circulating in Palestine. In contrast to international reports for the same season, A(H3N2) was not the dominant subtype as in northern hemisphere, nor was A(H1N1)pdm09 as in WHO reports for the Middle East, however genetic properties of Palestinian A(H3N2) and A(H1N1)pdm09 were in line with global isolates.


Assuntos
Variação Genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A/isolamento & purificação , Influenza Humana/epidemiologia , Epidemiologia Molecular , Neuraminidase/genética , RNA Viral/genética , Adolescente , Árabes/estatística & dados numéricos , Criança , Pré-Escolar , Monitoramento Epidemiológico , Evolução Molecular , Feminino , Humanos , Lactente , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Influenza Humana/sangue , Influenza Humana/virologia , Israel/epidemiologia , Masculino , Oriente Médio/epidemiologia , Filogenia , RNA Viral/sangue , Inquéritos e Questionários
12.
Emerg Microbes Infect ; 8(1): 479-485, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30924394

RESUMO

In late 2016, an H7N6 low pathogenic avian influenza virus outbreak occurred in domestic turkeys in Central Chile. We characterized the genetic and antigenic properties of the outbreak virus and its experimental transmission in chickens. Our studies demonstrate that the outbreak virus is a reassortment of genes identified from Chilean wild bird viruses between 2013 and 2017 and displays molecular adaptations to poultry and antiviral resistance to adamantanes. Further, these wild bird viruses are also able to transmit in experimentally infected chickens highlighting the need for continued surveillance and improvement of biosecurity in poultry farms.


Assuntos
Surtos de Doenças , Vírus da Influenza A/classificação , Vírus da Influenza A/isolamento & purificação , Influenza Aviária/epidemiologia , Influenza Aviária/virologia , Vírus Reordenados/classificação , Vírus Reordenados/isolamento & purificação , Adamantano/farmacologia , Adaptação Biológica , Animais , Animais Domésticos , Antivirais/farmacologia , Chile/epidemiologia , Farmacorresistência Viral , Vírus da Influenza A/genética , Vírus da Influenza A/imunologia , Vírus Reordenados/genética , Vírus Reordenados/imunologia , Perus
13.
Arch Virol ; 164(5): 1405-1410, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30847609

RESUMO

During the surveillance of avian influenza viruses in East Dongting Lake, China (2014-2015), two H11N8 avian influenza viruses were detected in the bean goose (Anser fabalis) and the falcated teal (Anas falcata). Phylogenetic analysis showed that these two novel reassortant H11N8 avian influenza viruses contain genes from poultry and wild birds. This is the first report detecting the H11N8 subtype influenza virus from wild birds in Asia. These findings indicate a dissemination of avian influenza virus along the East Asian-Australian flyway. In addition, the interaction between poultry and wild birds was addressed suggesting the need for intensive surveillance of wild bird populations.


Assuntos
Patos/virologia , Gansos/virologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/classificação , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A/isolamento & purificação , Neuraminidase/classificação , Neuraminidase/genética , Animais , Animais Selvagens/virologia , Aves/virologia , China , Genoma Viral/genética , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Influenza Aviária/virologia , Filogenia , Aves Domésticas/virologia , Vírus Reordenados/classificação , Vírus Reordenados/genética
14.
PLoS One ; 14(2): e0211553, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30785912

RESUMO

With rapidly increasing animal pathogen surveillance requirements, new technologies are needed for a comprehensive understanding of the roles of pathogens in the occurrence and development of animal diseases. We applied metagenomic technology to avian virus surveillance to study the main viruses infecting six poultry farms in two provinces in eastern China. Cloacal/throat double swabs were collected from 60 birds at each farm according to a random sampling method. The results showed that the method could simultaneously detect major viruses infecting farms, including avian influenza virus, infectious bronchitis virus, Newcastle disease virus, rotavirus G, duck hepatitis B virus, and avian leukemia virus subgroup J in several farms. The test results were consistent with the results from traditional polymerase chain reaction (PCR) or reverse transcription-PCR analyses. Five H9N2 and one H3N8 avian influenza viruses were detected at the farms and were identified as low pathogenic avian influenza viruses according to HA cleavage sites analysis. One detected Newcastle disease virus was classified as Class II genotype I and avirulent type according to F0 cleavage sites analysis. Three avian infectious bronchitis viruses were identified as 4/91, CK/CH/LSC/99I and TC07-2 genotypes by phylogenetic analysis of S1 genes. The viral infection surveillance method using metagenomics technology enables the monitoring of multiple viral infections, which allows the detection of main infectious viruses.


Assuntos
Monitoramento Epidemiológico/veterinária , Doenças das Aves Domésticas/virologia , Vírus de RNA/genética , Viroses/epidemiologia , Animais , Vírus da Bronquite Infecciosa/classificação , Vírus da Bronquite Infecciosa/genética , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Influenza Aviária/virologia , Metagenômica/métodos , Vírus da Doença de Newcastle/classificação , Vírus da Doença de Newcastle/genética , Filogenia , Aves Domésticas/virologia , Vírus de RNA/classificação , RNA Viral/química , Análise de Sequência de RNA , Viroses/virologia
15.
16.
Virology ; 530: 59-64, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30776509

RESUMO

Avian influenza A virus (AIV) has threatened global economy and public health. Wild birds have long been thought to serve as the natural reservoir of influenza virus, and thus it is expected that wild birds harbor higher viral diversity than poultry. Yet, this hypothesis has not been formally tested. Here, we assemble a data set of AIV from 75 regions worldwide over 11 years and compare the genetic diversity of wild bird AIV with that of poultry AIV. We find the genetic diversity of the internal genes of AIV in wild birds is not significantly higher than that in poultry. We propose that the unexpected diversity pattern of AIV internal genes could be explained by the synchronized global sweep of AIV internal genes occurring in the late 1800s and frequent AIV transmission between wild birds and poultry. Our findings might have important implications in understanding the evolution of influenza virus.


Assuntos
Aves , Variação Genética , Vírus da Influenza A/classificação , Vírus da Influenza A/isolamento & purificação , Influenza Aviária/virologia , Aves Domésticas , Animais , Saúde Global , Vírus da Influenza A/genética
17.
Virology ; 530: 11-18, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30753976

RESUMO

H5Nx clade 2.3.4.4 highly pathogenic avian influenza viruses (HPAIVs) have been disseminated to wide geographic regions since 2014. In 2016, five distinct genotypes (C-1 to C-5) of clade 2.3.4.4c H5N6 HPAIVs were detected in South Korea. In this study, we evaluated the pathogenicity, susceptibility to infection, and transmissibility of the two strains representing the C-1 and C-4 genotypes of the H5N6 viruses, which have different PA and NS gene, in domestic ducks. Although the susceptibility to infection of domestic ducks to the two strains was similar, the C-4 genotype virus induced higher mortality in ducks than C-1 genotype virus. A higher titer of viral shedding were detected in ducks challenged with the C-4 genotype virus compared with the C-1 genotype virus. These results indicated that the reassortment of HPAIVs with prevailing low pathogenic avian influenza viruses could effect on the pathogenicity in ducks.


Assuntos
Patos/virologia , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza A/patogenicidade , Influenza Aviária/virologia , RNA Replicase/genética , Proteínas não Estruturais Virais/genética , Proteínas Virais/genética , Animais , Variação Genética , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Influenza Aviária/mortalidade , Influenza Aviária/transmissão , Coreia (Geográfico) , Análise de Sobrevida , Eliminação de Partículas Virais
18.
EBioMedicine ; 40: 574-582, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30638863

RESUMO

BACKGROUND: VIS410, a broadly neutralizing monoclonal antibody that binds the hemagglutinin stem of influenza A viruses, was safe and efficacious in a human H1N1 virus challenge study. This study evaluated the safety and tolerability of VIS410 in non-hospitalized adult patients with uncomplicated influenza A. METHODS: Patients 18 to 65 years of age with symptom onset within 72 h were randomized 1:1:1 to receive a single intravenous infusion of VIS410 4000 mg, 2000 mg, or placebo. Neuraminidase inhibitor therapy was prohibited. Treatment-emergent adverse events (TEAEs) were evaluated up to 100 days post-infusion. Influenza symptoms were assessed daily for 10 days using the FLU-PRO tool. Nasopharyngeal virus shedding was assessed by quantitative reverse-transcription PCR (qRT-PCR) and viral culture through Day 7. FINDINGS: Of the 150 patients randomized, 148 received study drug, and 138 were confirmed influenza A positive. Median age was 42 years; median time from symptom onset to treatment was 42 h; 93% had influenza A subtype H3N2. SAFETY: TEAEs, most commonly diarrhea of mild severity, were dose-related, occurring in 55%, 35%, and 24% of the 4000 mg, 2000 mg, and placebo patients, respectively. Two serious adverse events occurred, both in placebo patients. SYMPTOM ANALYSES: Baseline FLU-PRO symptom scores were balanced among groups. Mean scores were lower by Days 3 and 4 in the pooled VIS410 treatment group versus placebo (p < 0.023), with a tendency toward faster resolution by Kaplan-Meier analysis. VIROLOGY ANALYSES: VIS410 was associated with reduced median nasopharyngeal viral load TCID50 AUCDay7 (days × log10 TCID50/mL) (3.66 pooled VIS410 vs 4.78 placebo, p = 0.08) and in the subset of patients with baseline hemagglutination inhibition (HAI) titer ≤40 (overall, 74% of patients) was significantly reduced vs placebo (4.218 pooled VIS410 vs 6.152 placebo, p = 0.009). Kaplan-Meier estimated time to resolution of viral shedding was reduced (1.9 vs 3.6 days, p = 0.03) in VIS410 treated patients. There was a trend toward greater proportion of culture-negative patients by Day 3 (66.7% vs 51.1%, p = 0.11); when this analysis was limited to the subset of patients with positive baseline cultures, this difference became more pronounced (63.2% vs 42.5%, p = 0.053). No differences were observed in nasopharyngeal influenza qRT-PCR profiles, which represent both live and neutralized virus. INTERPRETATION: VIS410 was safe and well tolerated in adults with uncomplicated influenza A, with favorable effects on symptom resolution and virus replication. TRIAL REGISTRATION: Clinical Trials: NCT02989194. FUNDING: This project was funded in part with Federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA), under Contract No. HHSO100201500018C.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Antivirais/uso terapêutico , Vírus da Influenza A , Influenza Humana/tratamento farmacológico , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Antivirais/administração & dosagem , Anticorpos Antivirais/uso terapêutico , Antivirais/administração & dosagem , Feminino , Humanos , Imunoterapia , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Vírus da Influenza A/imunologia , Influenza Humana/diagnóstico , Influenza Humana/imunologia , Influenza Humana/virologia , Masculino , Avaliação de Sintomas , Resultado do Tratamento , Carga Viral , Eliminação de Partículas Virais/efeitos dos fármacos
19.
Emerg Infect Dis ; 25(2): 333-337, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30666923

RESUMO

Screening of 533 bats for influenza A viruses showed subtype HL18NL11 in intestines of 2 great fruit-eating bats (Artibeus lituratus). High concentrations suggested fecal shedding. Genomic characterizations revealed conservation of viral genes across different host species, countries, and sampling years, suggesting a conserved cellular receptor and wide-ranging occurrence of bat influenza A viruses.


Assuntos
Quirópteros/virologia , Vírus da Influenza A , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/virologia , Animais , Brasil/epidemiologia , Genoma Viral , Genômica/métodos , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Filogenia , Relação Estrutura-Atividade , Proteínas Virais/química , Proteínas Virais/genética
20.
Influenza Other Respir Viruses ; 13(3): 262-273, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-29624873

RESUMO

BACKGROUND: Regular spatial and temporal analyses of the genetic diversity and evolutionary patterns of influenza A virus (IAV) in swine inform control efforts and improve animal health. Initiated in 2009, the USDA passively surveils IAV in U.S. swine, with a focus on subtyping clinical respiratory submissions, sequencing the hemagglutinin (HA) and neuraminidase (NA) genes at a minimum, and sharing these data publicly. OBJECTIVES: In this study, our goal was to quantify and describe regional and national patterns in the genetic diversity and evolution of IAV in U.S. swine from 2010 to 2016. METHODS: A comprehensive phylogenetic and epidemiological analysis of publicly available HA and NA genes generated by the USDA surveillance system collected from January 2010 to December 2016 was conducted. RESULTS: The dominant subtypes and genetic clades detected during the study period were H1N1 (H1-γ/1A.3.3.3, N1-classical, 29%), H1N2 (H1-δ1/1B.2.2, N2-2002, 27%), and H3N2 (H3-IV-A, N2-2002, 15%), but many other minor clades were also maintained. Year-round circulation was observed, with a primary epidemic peak in October-November and a secondary epidemic peak in March-April. Partitioning these data into 5 spatial zones revealed that genetic diversity varied regionally and was not correlated with aggregated national patterns of HA/NA diversity. CONCLUSIONS: These data suggest that vaccine composition and control efforts should consider IAV diversity within swine production regions in addition to aggregated national patterns.


Assuntos
Variação Genética , Vírus da Influenza A/classificação , Vírus da Influenza A/isolamento & purificação , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/virologia , Filogeografia , Animais , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Epidemiologia Molecular , Neuraminidase/genética , Filogenia , Estações do Ano , Análise de Sequência de DNA , Análise Espaço-Temporal , Suínos , Estados Unidos/epidemiologia , Proteínas Virais/genética
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