RESUMEN
We isolated highly pathogenic avian influenza (HPAI) H5N5 and H5N1 viruses from crows in Hokkaido, Japan, during winter 2023-24. They shared genetic similarity with HPAI H5N5 viruses from northern Europe but differed from those in Asia. Continuous monitoring and rapid information sharing between countries are needed to prevent HPAI virus transmission.
RESUMEN
High pathogenicity avian influenza viruses (HPAIVs) of the H5N1 and H5N2 subtypes were responsible for 84 HPAI outbreaks on poultry premises in Japan during October 2022-April 2023. The number of outbreaks during the winter of 2022-2023 is the largest ever reported in Japan. In this study, we performed phylogenetic analyses using the full genetic sequences of HPAIVs isolated in Japan during 2022-2023 and those obtained from a public database to identify their genetic origin. Based on the hemagglutinin genes, these HPAIVs were classified into the G2 group of clade 2.3.4.4b, whose ancestors were H5 HPAIVs that circulated in Europe in late 2020, and were then further divided into three subgroups (G2b, G2d, and G2c). Approximately one-third of these viruses were classified into the G2b and G2d groups, which also included H5N1 HPAIVs detected in Japan during 2021-2022. In contrast, the remaining two-thirds were classified into the G2c group, which originated from H5N1 HPAIVs isolated in Asian countries and Russia during the winter of 2021-2022. Unlike the G2b and G2d viruses, the G2c viruses were first detected in Japan in the fall of 2022. Importantly, G2c viruses caused the largest number of outbreaks throughout Japan over the longest period during the season. Phylogenetic analyses using eight segment genes revealed that G2b, G2d, and G2c viruses were divided into 2, 4, and 11 genotypes, respectively, because they have various internal genes closely related to those of avian influenza viruses detected in wild birds in recent years in Asia, Russia, and North America, respectively. These results suggest that HPAIVs were disseminated among migratory birds, which may have generated numerous reassortant viruses with various gene constellations, resulting in a considerable number of outbreaks during the winter of 2022-2023.
Asunto(s)
Brotes de Enfermedades , Variación Genética , Subtipo H5N1 del Virus de la Influenza A , Subtipo H5N2 del Virus de la Influenza A , Gripe Aviar , Filogenia , Aves de Corral , Animales , Japón/epidemiología , Gripe Aviar/virología , Gripe Aviar/epidemiología , Aves de Corral/virología , Subtipo H5N1 del Virus de la Influenza A/genética , Subtipo H5N1 del Virus de la Influenza A/patogenicidad , Subtipo H5N1 del Virus de la Influenza A/clasificación , Subtipo H5N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H5N2 del Virus de la Influenza A/genética , Subtipo H5N2 del Virus de la Influenza A/patogenicidad , Subtipo H5N2 del Virus de la Influenza A/aislamiento & purificación , Subtipo H5N2 del Virus de la Influenza A/clasificación , Brotes de Enfermedades/veterinaria , Enfermedades de las Aves de Corral/virología , Enfermedades de las Aves de Corral/epidemiología , Estaciones del Año , Glicoproteínas Hemaglutininas del Virus de la Influenza/genéticaRESUMEN
In winter 2021-2022, H5N1 and H5N8 high-pathogenicity avian influenza (HPAI) viruses (HPAIVs) caused serious outbreaks in Japan: 25 outbreaks of HPAI at poultry farms and 107 cases in wild birds or in the environment. Phylogenetic analyses divided H5 HPAIVs isolated in Japan in the winter of 2021-2022 into three groups-G2a, G2b, and G2d-which were disseminated at different locations and times. Full-genome sequencing analyses of these HPAIVs revealed a strong relationship of multiple genes between Japan and Siberia, suggesting that they arose from reassortment events with avian influenza viruses (AIVs) in Siberia. The results emphasize the complex of dissemination and reassortment events with the movement of migratory birds, and the importance of continual monitoring of AIVs in Japan and Siberia for early alerts to the intrusion of HPAIVs.
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Subtipo H5N1 del Virus de la Influenza A , Subtipo H5N8 del Virus de la Influenza A , Virus de la Influenza A , Gripe Aviar , Animales , Gripe Aviar/epidemiología , Subtipo H5N1 del Virus de la Influenza A/genética , Japón/epidemiología , Filogenia , Virulencia , Aves , Animales Salvajes , Virus de la Influenza A/genéticaRESUMEN
During the winter of 2020-2021, numerous outbreaks of high pathogenicity avian influenza (HPAI) were caused by viruses of the subtype H5N8 in poultry over a wide region in Japan. The virus can be divided into five genotypes-E1, E2, E3, E5, and E7. The major genotype responsible for the outbreaks was E3, followed by E2. To investigate the cause of these outbreaks, we experimentally infected chickens with five representative strains of each genotype. We found that the 50% chicken infectious dose differed by up to 75 times among the five strains, and the titer of the E3 strains (102.75 50% egg infectious dose (EID50)) was the lowest, followed by that of the E2 strains (103.50 EID50). In viral transmission experiments, in addition to the E3 and E2 strains, the E5 strain was transmitted to naïve chickens with high efficiency (>80%), whereas the other strains had low efficiencies (<20%). We observed a clear difference in the virological characteristics among the five strains isolated in the same season. The higher infectivity of the E3 and E2 viruses in chickens may have caused the large number of HPAI outbreaks in Japan during this season.
Asunto(s)
Subtipo H5N8 del Virus de la Influenza A , Gripe Aviar , Enfermedades de las Aves de Corral , Animales , Pollos , Subtipo H5N8 del Virus de la Influenza A/genética , Virulencia , Japón/epidemiología , Estaciones del Año , Brotes de Enfermedades/veterinariaRESUMEN
H5N8 and H5N1 high pathogenicity avian influenza viruses (HPAIVs) caused outbreaks in poultry farms in Japan from November 2021 to May 2022. Hemagglutinin genes of these viruses belong to clade 2.3.4.4B and can be divided phylogenetically into the following groups: 20A, 20E, and 21E. In this study, we compared the infectivity and transmissibility of HPAIVs from three groups of chickens. Representative strains from 20A, 20E, and 21E groups are A/chicken/Akita/7C/2021(H5N8)(Akita7C), A/chicken/Kagoshima/21A6T/2021(H5N1)(Kagoshima6T), and A/chicken/Iwate/21A7T/2022(H5N1)(Iwate7T), respectively. Fifty percent lethal dose of Akita7C in chickens (103.83 fifty percent egg infectious dose (EID50)) was up to seven times lower than those of Kagoshima6T and Iwate7T (104.50 and 104.68 EID50, respectively). Mean death times for Akita7C- and Kagoshima6T-infected chickens (3.45 and 3.30 days, respectively) were at least a day longer than that of Iwate7T (2.20 days). Viral titers of the trachea and cloaca of Iwate7T-infected chicken were the highest detected. The transmission rate of the Akita7C strain (100%) was markedly higher than those of the two strains (<50%). These data suggest that the infectivity and transmissibility of the Akita7C strain (H5N8) in chickens are higher than those of H5N1 viruses, providing fundamental information needed for formulating effective prevention and control strategies for HPAI outbreaks.
Asunto(s)
Subtipo H5N1 del Virus de la Influenza A , Subtipo H5N8 del Virus de la Influenza A , Virus de la Influenza A , Gripe Aviar , Animales , Pollos , Subtipo H5N1 del Virus de la Influenza A/genética , Japón/epidemiología , Subtipo H5N8 del Virus de la Influenza A/genética , Estaciones del Año , Virulencia , Gripe Aviar/epidemiologíaRESUMEN
Genetic analyses of highly pathogenic avian influenza H5 subtype viruses isolated from the Izumi Plain, Japan, revealed cocirculation of 2 genetic groups of clade 2.3.4.4b viruses among migratory waterfowl. Our findings demonstrate that both continuous surveillance and timely information sharing of avian influenza viruses are valuable for rapid risk assessment.
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Subtipo H5N1 del Virus de la Influenza A , Subtipo H5N2 del Virus de la Influenza A , Subtipo H5N8 del Virus de la Influenza A , Virus de la Influenza A , Gripe Aviar , Gripe Humana , Enfermedades de las Aves de Corral , Animales , Animales Salvajes , Aves , Humanos , Subtipo H5N2 del Virus de la Influenza A/genética , Subtipo H5N8 del Virus de la Influenza A/genética , Virus de la Influenza A/genética , Gripe Aviar/epidemiología , Japón/epidemiología , Filogenia , Aves de Corral , Enfermedades de las Aves de Corral/epidemiologíaRESUMEN
Swine influenza (SI) is a major respiratory disease of swine; SI is due to the influenza A virus of swine (IAV-S), a highly contagious virus with zoonotic potential. The intensity of IAV-S surveillance varies among countries because it is not a reportable disease and causes limited mortality in swine. Although Asia accounts for half of all pig production worldwide, SI is not well managed in those countries. Rigorously managing SI on pig farms could markedly reduce the economic losses, the likelihood of novel reassortants among IAV-S, and the zoonotic IAV-S infections in humans. Vaccination of pigs is a key control measure for SI, but its efficacy relies on the optimal antigenic matching of vaccine strains with the viral strains circulating in the field. Here, we phylogenetically reviewed the genetic diversity of the hemagglutinin gene among IAVs-S that have circulated in Asia during the last decade. This analysis revealed the existence of country-specific clades in both the H1 and H3 subtypes and cross-border transmission of IAVs-S. Our findings underscore the importance of choosing vaccine antigens for each geographic region according to both genetic and antigenic analyses of the circulating IAV-S to effectively manage SI in Asia.
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Virus de la Influenza A , Gripe Humana , Infecciones por Orthomyxoviridae , Enfermedades de los Porcinos , Animales , Variación Genética , Hemaglutininas/genética , Humanos , Subtipo H3N2 del Virus de la Influenza A/genética , Virus de la Influenza A/genética , Filogenia , PorcinosRESUMEN
Poly(N-vinylacetamide-co-acrylic acid) coupled with d-octaarginine (VP-R8) promotes the cellular uptake of peptides/proteins in vitro; however, details of the transfection efficacy of VP-R8, such as the cell types possessing high gene transfer, are not known. Herein, we compared the ability of VP-R8 to induce the cellular uptake of plasmid DNA in mouse and human cell lines from different tissues and organs. A green fluorescent protein (GFP)-expression plasmid was used as model genetic material, and fluorescence as an indicator of uptake and plasmid-derived protein expression. Three mouse and three human cell lines were incubated with a mixture of plasmid and VP-R8, and fluorescence analysis were performed two days after transfection. To confirm stable transgene expression, we performed drug selection three days after transfection. A commercially available polymer-based DNA transfection reagent (PTR) was used as the transfection control and standard for comparing transgene expression efficiency. In the case of transient transgene expression, slight-to-moderate GFP expression was observed in all cell lines transfected with plasmid via VP-R8; however, transfection efficiency was lower than using the PTR for gene delivery. In the case of stable transgene expression, VP-R8 promoted drug-resistance acquisition more efficiently than the PTR did. Cells that developed drug resistance after VP-R8-mediated gene transfection expressed GFP more efficiently than cells that developed drug resistance after transfection with the PTR. Thus, VP-R8 shows potential as an in vitro or ex vivo nonviral transfection tool for generating cell lines with stable transgene expression.
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ADN , Polímeros , Animales , Línea Celular , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Ratones , Oligopéptidos , Plásmidos/genética , Transfección/veterinaria , TransgenesRESUMEN
The circulation of avian influenza A viruses in poultry is a public health concern due to the potential transmissibility and severity of these viral infections. Monitoring the susceptibility of these viruses to antivirals is important for developing measures to strengthen the level of preparedness against influenza pandemics. However, drug susceptibility information on these viruses is limited. Here, we determined the susceptibilities of avian influenza A(H5N1), A(H5N2), A(H5N8), A(H7N7), A(H7N9), A(H9N1), and A(H9N2) viruses isolated in Japan to the antivirals approved for use there: an M2 inhibitor (amantadine), neuraminidase inhibitors (oseltamivir, peramivir, zanamivir, and laninamivir) and RNA polymerase inhibitors (baloxavir and favipiravir). Genotypic methods that detect amino acid substitutions associated with antiviral resistance and phenotypic methods that assess phenotypic viral susceptibility to drugs have revealed that these avian influenza A viruses are susceptible to neuraminidase and RNA polymerase inhibitors. These results suggest that neuraminidase and RNA polymerase inhibitors currently approved in Japan could be a treatment option against influenza A virus infections in humans.
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Farmacorresistencia Viral , Gripe Aviar , Gripe Humana , Animales , Antivirales/farmacología , Antivirales/uso terapéutico , ARN Polimerasas Dirigidas por ADN , Farmacorresistencia Viral/genética , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Humanos , Subtipo H5N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H5N2 del Virus de la Influenza A/efectos de los fármacos , Subtipo H7N7 del Virus de la Influenza A/efectos de los fármacos , Subtipo H7N9 del Virus de la Influenza A/efectos de los fármacos , Subtipo H9N2 del Virus de la Influenza A/efectos de los fármacos , Gripe Aviar/epidemiología , Gripe Aviar/virología , Gripe Humana/epidemiología , Gripe Humana/virología , Japón/epidemiología , Neuraminidasa/genética , Neuraminidasa/metabolismo , Oseltamivir/farmacología , Oseltamivir/uso terapéutico , Aves de CorralRESUMEN
High pathogenic avian influenza viruses (HPAIVs) of the H5 subtype have spread in poultry and wild birds worldwide. Current studies have highlighted the association between the migration of wild birds and the spread of HPAIVs. However, virological studies examining responsible species of migratory birds to spread HPAIVs are limited. In Japan, the common teal (Anas crecca) arrives in great numbers for overwintering every autumn-spring season; therefore, we performed experimental infection using six H5 HPAIVs isolated in past outbreaks in Japan (A/chicken/Yamaguchi/7/2004 (H5N1), A/whooper swan/Akita/1/2008 (H5N1), A/mandarin duck/Miyazaki/22M-765/2011 (H5N1), A/duck/Chiba/26-372-48/2014 (H5N8), A/duck/Hyogo/1/2016 (H5N6) and A/mute swan/Shimane/3211A002/2017 (H5N6)) to evaluate the susceptibility of the species to HPAIV infection. The results illustrated that most birds in all experimental groups were infected by the strains, and they shed viruses for a prolonged period, in trachea than cloaca, without displaying distinctive clinical signs. In addition, comparative analysis using calculation value of total viral shedding during the experiment revealed that the birds shed viruses at above a certain level regardless of the differences of strains. These results suggested that the common teal could be a migratory bird species that disseminates viruses in the environment, thereby influencing HPAI outbreaks in wild birds in Japan.
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Susceptibilidad a Enfermedades , Patos , Virus de la Influenza A , Gripe Aviar , Animales , Susceptibilidad a Enfermedades/veterinaria , Susceptibilidad a Enfermedades/virología , Patos/virología , Virus de la Influenza A/patogenicidad , Virus de la Influenza A/fisiología , Gripe Aviar/virología , JapónRESUMEN
The aim of this study was to investigate the sensitivity of three breeds of Japanese native chickens, commercial broilers, and specific-pathogen-free (SPF) white leghorns to three strains of the H5 subtype of highly pathogenic avian influenza viruses (HPAIVs). Chickens were experimentally inoculated with doses of 102, 104, and 106 50% egg infective dose of A/mandarin duck/Miyazaki/22M-765/2011 (duck-11), A/chicken/Miyazaki/7/2014 (chicken-14), and A/chicken/Kumamoto/1-2C/2016 (chicken-16). The 50% chicken lethal dose of each virus, mean death time, and viral shedding patterns were compared. The Japanese native chickens showed varied susceptibility to the three H5 HPAIV isolates. Although two of the breeds showed some degree of resistance to duck-11 and chicken-14, all three were more sensitive to chicken-16 than commercial broiler chickens. We have shown that Japanese native chickens do not necessarily have resistance to HPAIV and that the pathogenic characteristics of HPAIVs are quite different between native and commercial chickens.
Nota de investigaciónDiferente sensibilidad de pollos nativos de Japón a subtipos del virus de influenza aviar H5 altamente patógenos. El objetivo de este estudio fue investigar la sensibilidad de tres razas de pollos nativos de Japón, de pollos de engorde comerciales y de aves Leghorn blancas libres de patógenos específicos (SPF) a tres cepas altamente patógenas del virus de influenza aviar (HPAIV) del subtipo H5. Los pollos se inocularon experimentalmente con dosis de 102, 104 y 106 dosis infecciosas para embrión de pollo 50% del virus A/pato mandarín/Miyazaki/22M-765/2011 (pato-11), del virus A/pollo/Miyazaki/7/2014 (pollo-14) y A/ pollo/Kumamoto/1-2C-2016 (pollo-16). Se comparó la dosis letal de pollo 50% de cada virus, el tiempo medio de muerte y los patrones de diseminación viral. Los pollos nativos japoneses mostraron una susceptibilidad variada a los tres aislados del virus de influenza aviar altamente patógeno H5. Aunque dos de las razas mostraron cierto grado de resistencia al virus de pato-11 y al pollo-14, las tres eran más sensibles al virus del pollo-16 que los pollos de engorde comerciales. Se demostró que los pollos nativos japoneses no necesariamente tienen resistencia al virus de influenza aviar altamente patógeno y que las características patógenas de los virus de influenza aviar altamente patógenos son bastante diferentes entre pollos nativos y comerciales.
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Virus de la Influenza A , Gripe Aviar , Animales , Pollos , Patos , JapónRESUMEN
On 5 November 2020, a confirmed outbreak due to an H5N8 highly pathogenic avian influenza virus (HPAIV) occurred at an egg-hen farm in Kagawa prefecture (western Japan). This virus, A/chicken/Kagawa/11C/2020 (Kagawa11C2020), was the first HPAI poultry isolate in Japan in 2020 and had multiple basic amino acids-a motif conferring high pathogenicity to chickens-at the hemagglutinin cleavage site. Mortality of chickens was 100% through intravenous inoculation tests performed according to World Organization for Animal Health criteria. Phylogenetic analysis showed that the hemagglutinin of Kagawa11C2020 belongs to clade 2.3.4.4B of the H5 Goose/Guangdong lineage and clusters with H5N8 HPAIVs isolated from wild bird feces collected in Hokkaido (Japan) and Korea in October 2020. These H5N8 HPAIVs are closely related to H5N8 HPAIVs isolated in European countries during the winter of 2019-2020. Intranasal inoculation of chickens with 106 fifty-percent egg infectious doses of Kagawa11C2020 revealed that the 50% chicken lethal dose was 104.63 and the mean time to death was 134.4 h. All infected chickens demonstrated viral shedding beginning on 2 dpi-before clinical signs were observed. These results suggest that affected chickens could transmit Kagawa11C2020 to surrounding chickens in the absence of clinical signs for several days before they died.
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Pollos/virología , Brotes de Enfermedades/veterinaria , Subtipo H5N8 del Virus de la Influenza A/aislamiento & purificación , Gripe Aviar/epidemiología , Enfermedades de las Aves de Corral/epidemiología , Animales , Japón/epidemiologíaRESUMEN
INTRODUCTION: The concept of continuum of care has gained attention as measures to improve maternal, newborn, and child health. However, little is known about the factors associated with the coverage level of continuum of care in Lao PDR. Therefore, this study was conducted 1) to investigate the coverage level of continuum of care and 2) to identify barriers and promoting factors that are associated with mothers' continuation in receiving services in rural Lao PDR. METHODS: A community-based, cross sectional study was conducted in a rural district in Khammouane Province, Lao PDR, using a structured questionnaire. The outcome to the express continuum of care was assessed by the modified composite coverage index (CCI) that reflects ten maternal and child health services. RESULTS: In total, 263 mothers were included in the final analyses. Only 6.8% of mothers continued to receive all MNCH services. Five factors were shown to have statistically significant associations with modified CCI score: higher educational attainment (B = 0.070, p<0.001), being a farmer (B = -0.078, p = 0.003), receiving the first antenatal care within the first trimester (B = 0.109, p<0.001), longer distance from district hospital (B = -0.012, p<0.001), and discussion with husband or family members (B = 0.057, p = 0.022). CONCLUSIONS: In this study, we introduced the modified CCI to better explain the utilization of preventive maternal and child health services along with the continuum of care. By utilizing the modified CCI, we identified five factors as determinants of continuum of care. Furthermore, new and modifiable promoting factors were identified for continuum of care: receiving the first antenatal care within the first trimester and family and male involvement. Such demand side actions should be encouraged to improve the continuity of MNCH service use.
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Continuidad de la Atención al Paciente/estadística & datos numéricos , Servicios de Salud Materno-Infantil/organización & administración , Servicios Preventivos de Salud/organización & administración , Servicios de Salud Rural/organización & administración , Adulto , Salud Infantil , Estudios Transversales , Femenino , Humanos , Lactante , Laos , Masculino , Salud Materna , Servicios de Salud Materno-Infantil/estadística & datos numéricos , Embarazo , Servicios Preventivos de Salud/estadística & datos numéricos , Servicios de Salud Rural/estadística & datos numéricos , Población Rural/estadística & datos numéricos , Factores Socioeconómicos , Adulto JovenRESUMEN
PURPOSE: Patients with cervical cancer recurrence after concurrent chemoradiotherapy (CCRT) who are not candidates for surgical resection or salvage radiotherapy have a dismal prognosis. The predictive factors for the effects of chemotherapy and prognostic factors in these patients were analyzed. METHODS: We collected data for patients with recurrent cervical cancer who were primarily treated with CCRT between 2000 and 2013. Among them, 57 patients treated with only systemic chemotherapy were analyzed for the overall survival (OS), the overall response rate (ORR), and prognostic factors. RESULTS: The median age was 47 years. Inside the irradiated field recurrence occurred in 24, outside in 20 and both in 13 patients. Time to recurrence after the CCRT (i.e., therapy-free interval; TFI) were <6 months in 11, 6-12 months in 15, ≥12 months in 23 patients, and persistent disease in 8 patients. The median OS was 18 months and ORR was 15.7%. Those with a longer TFI showed a tendency for better ORR (p = 0.051) and those receiving a taxane-containing regimen showed significantly higher ORR (p = 0.0232). Multivariate analysis revealed a significant correlation between the median OS and TFI (HR = 4.688, 95% CI = 2.178-11.10, p < 0.0001) and chemotherapy response (HR = 20.08, 95% CI = 3.936-368.4, p < 0.0001). Furthermore, even in patients with stable disease, the median OS increased corresponding to the length of the TFI (p < 0.0001). CONCLUSIONS: TFI has predictive value for response to chemotherapy and prognosis of patients with recurrent cervical cancer after definitive CCRT.