Different environmental drivers of highly pathogenic avian influenza H5N1 outbreaks in poultry and wild birds

NARCIS (Netherlands)

Si, Y.; Boer, de W.F.; Gong, P.

2013-01-01

A large number of highly pathogenic avian influenza (HPAI) H5N1 outbreaks in poultry and wild birds have been reported in Europe since 2005. Distinct spatial patterns in poultry and wild birds suggest that different environmental drivers and potentially different spread mechanisms are operating.

Genetic and phylogenetic characterizations of a novel genotype of highly pathogenic avian influenza (HPAI) H5N8 viruses in 2016/2017 in South Korea.

Science.gov (United States)

Kim, Young-Il; Park, Su-Jin; Kwon, Hyeok-Il; Kim, Eun-Ha; Si, Young-Jae; Jeong, Ju-Hwan; Lee, In-Won; Nguyen, Hiep Dinh; Kwon, Jin-Jung; Choi, Won Suk; Song, Min-Suk; Kim, Chul-Joong; Choi, Young-Ki

2017-09-01

During the outbreaks of highly pathogenic avian influenza (HPAI) H5N6 viruses in 2016 in South Korea, novel H5N8 viruses were also isolated from migratory birds. Phylogenetic analysis revealed that the HA gene of these H5N8 viruses belonged to clade 2.3.4.4, similarly to recent H5Nx viruses, and originated from A/Brk/Korea/Gochang1/14(H5N8), a minor lineage of H5N8 that appeared in 2014 and then disappeared. At least four reassortment events occurred with different subtypes (H5N8, H7N7, H3N8 and H10N7) and a chicken challenge study revealed that they were classified as HPAI viruses according to OIE criteria. Copyright © 2017 Elsevier B.V. All rights reserved.

Victims and vectors: highly pathogenic avian influenza H5N1 and the ecology of wild birds

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Takekawa, John Y.; Prosser, Diann J.; Newman, Scott H.; Muzaffar, Sabir Bin; Hill, Nichola J.; Yan, Baoping; Xiao, Xiangming; Lei, Fumin; Li, Tianxian; Schwarzbach, Steven E.; Howell, Judd A.

2010-01-01

The emergence of highly pathogenic avian influenza (HPAI) viruses has raised concerns about the role of wild birds in the spread and persistence of the disease. In 2005, an outbreak of the highly pathogenic subtype H5N1 killed more than 6,000 wild waterbirds at Qinghai Lake, China. Outbreaks have continued to periodically occur in wild birds at Qinghai Lake and elsewhere in Central China and Mongolia. This region has few poultry but is a major migration and breeding area for waterbirds in the Central Asian Flyway, although relatively little is known about migratory movements of different species and connectivity of their wetland habitats. The scientific debate has focused on the role of waterbirds in the epidemiology, maintenance and spread of HPAI H5N1: to what extent are they victims affected by the disease, or vectors that have a role in disease transmission? In this review, we summarise the current knowledge of wild bird involvement in the ecology of HPAI H5N1. Specifically, we present details on: (1) origin of HPAI H5N1; (2) waterbirds as LPAI reservoirs and evolution into HPAI; (3) the role of waterbirds in virus spread and persistence; (4) key biogeographic regions of outbreak; and (5) applying an ecological research perspective to studying AIVs in wild waterbirds and their ecosystems.

2.1 Natural History of Highly Pathogenic Avian Influenza H5N1

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Sonnberg, Stephanie; Webby, Richard J.; Webster, Robert G.

2013-01-01

The ecology of highly pathogenic avian influenza (HPAI) H5N1 has significantly changed from sporadic outbreaks in terrestrial poultry to persistent circulation in terrestrial and aquatic poultry and potentially in wild waterfowl. A novel genotype of HPAI H5N1 arose in 1996 in southern China and through ongoing mutation, reassortment, and natural selection, has diverged into distinct lineages and expanded into multiple reservoir hosts. The evolution of Goose/Guangdong-lineage highly pathogenic H5N1 viruses is ongoing: while stable interactions exist with some reservoir hosts, these viruses are continuing to evolve and adapt to others, and pose an un-calculable risk to sporadic hosts, including humans. PMID:23735535

Seroprevalence of antibodies against highly pathogenic avian influenza A (H5N1 virus among poultry workers in Bangladesh, 2009.

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Sharifa Nasreen

Full Text Available We conducted a cross-sectional study in 2009 to determine the seroprevalence and risk factors for highly pathogenic avian influenza A (H5N1 [HPAI H5N1] virus antibodies among poultry workers at farms and live bird markets with confirmed/suspected poultry outbreaks during 2009 in Bangladesh. We tested sera by microneutralization assay using A/Bangladesh/207095/2008 (H5N1; clade 2.2.2 virus with confirmation by horse red blood cell hemagglutination inhibition and H5-specific Western blot assays. We enrolled 212 workers from 87 farms and 210 workers from three live bird markets. One hundred and two farm workers (48% culled poultry. One hundred and ninety-three farm workers (91% and 178 market workers (85% reported direct contact with poultry that died during a laboratory confirmed HPAI H5N1 poultry farm outbreak or market poultry die-offs from suspected HPAI H5N1. Despite exposure to sick poultry, no farm or market poultry workers were seropositive for HPAI H5N1 virus antibodies (95% confidence interval 0-1%.

Effect of species, breed and route of virus inoculation on the pathogenicity of H5N1 highly pathogenic influenza (HPAI) viruses in domestic ducks.

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Pantin-Jackwood, Mary; Swayne, David E; Smith, Diane; Shepherd, Eric

2013-07-22

H5N1 highly pathogenic avian influenza (HPAI) viruses continue to be a threat to poultry in many regions of the world. Domestic ducks have been recognized as one of the primary factors in the spread of H5N1 HPAI. In this study we examined the pathogenicity of H5N1 HPAI viruses in different species and breeds of domestic ducks and the effect of route of virus inoculation on the outcome of infection. We determined that the pathogenicity of H5N1 HPAI viruses varies between the two common farmed duck species, with Muscovy ducks (Cairina moschata) presenting more severe disease than various breeds of Anas platyrhynchos var. domestica ducks including Pekin, Mallard-type, Black Runners, Rouen, and Khaki Campbell ducks. We also found that Pekin and Muscovy ducks inoculated with two H5N1 HPAI viruses of different virulence, given by any one of three routes (intranasal, intracloacal, or intraocular), became infected with the viruses. Regardless of the route of inoculation, the outcome of infection was similar for each species but depended on the virulence of the virus used. Muscovy ducks showed more severe clinical signs and higher mortality than the Pekin ducks. In conclusion, domestic ducks are susceptible to H5N1 HPAI virus infection by different routes of exposure, but the presentation of the disease varied by virus strain and duck species. This information helps support the planning and implementation of H5N1 HPAI surveillance and control measures in countries with large domestic duck populations.

Public health concerns of highly pathogenic avian influenza H5N1 endemicity in Africa

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Olubunmi Gabriel Fasanmi

2017-10-01

Full Text Available Highly pathogenic avian influenza virus (HPAIV H5N1 was first officially reported in Africa in 2006; thereafter this virus has spread rapidly from Nigeria to 11 other African countries. This study was aimed at utilizing data from confirmed laboratory reports to carry out a qualitative evaluation of the factors responsible for HPAI H5N1 persistence in Africa and the public health implications; and to suggest appropriate control measures. Relevant publications were sought from data banks and repositories of FAO, OIE, WHO, and Google scholars. Substantiated data on HPAI H5N1 outbreaks in poultry in Africa and in humans across the world were mined. HPAI H5N1 affects poultry and human populations, with Egypt having highest human cases (346 globally. Nigeria had a reinfection from 2014 to 2015, with outbreaks in Cote d'Ivoire, Ghana, Niger, Nigeria, and Burkina Faso throughout 2016 unabated. The persistence of this virus in Africa is attributed to the survivability of HPAIV, ability to evolve other subtypes through genetic reassortment, poor biosecurity compliance at the live bird markets and poultry farms, husbandry methods and multispecies livestock farming, poultry vaccinations, and continuous shedding of HPAIV, transboundary transmission of HPAIV through poultry trades; and transcontinental migratory birds. There is, therefore, the need for African nations to realistically reassess their status, through regular surveillance and be transparent with HPAI H5N1 outbreak data. Also, it is important to have an understanding of HPAIV migration dynamics which will be helpful in epidemiological modeling, disease prevention, control and eradication measures.

Sensitization with vaccinia virus encoding H5N1 hemagglutinin restores immune potential against H5N1 influenza virus.

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Yasui, Fumihiko; Itoh, Yasushi; Ikejiri, Ai; Kitabatake, Masahiro; Sakaguchi, Nobuo; Munekata, Keisuke; Shichinohe, Shintaro; Hayashi, Yukiko; Ishigaki, Hirohito; Nakayama, Misako; Sakoda, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa; Kohara, Michinori

2016-11-28

H5N1 highly pathogenic avian influenza (H5N1 HPAI) virus causes elevated mortality compared with seasonal influenza viruses like H1N1 pandemic influenza (H1N1 pdm) virus. We identified a mechanism associated with the severe symptoms seen with H5N1 HPAI virus infection. H5N1 HPAI virus infection induced a decrease of dendritic cell number in the splenic extrafollicular T-cell zone and impaired formation of the outer layers of B-cell follicles, resulting in insufficient levels of antibody production after infection. However, in animals vaccinated with a live recombinant vaccinia virus expressing the H5 hemagglutinin, infection with H5N1 HPAI virus induced parafollicular dendritic cell accumulation and efficient antibody production. These results indicate that a recombinant vaccinia encoding H5 hemagglutinin gene does not impair dendritic cell recruitment and can be a useful vaccine candidate.

TEST KIT FOR THE DETECTION AND GENOTYPING OF HIGHLY PATHOGENIC INFLUENZA VIRUS A H5N1 BY REAL-TIME POLYMERASE CHAIN REACTION

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S. V. Stepaniuk

2014-06-01

Full Text Available Results of the annual monitoring of epizooties indicate that highly pathogenic HPAI/H5N1 avian influenza widely circulated in Eurasian region. Over a period of 2010–2013 years more than 165 cases of outbreaks in 14 countries were found out. Ukraine became one of the first countries in Europe where in Autonomous Republic of Crimea in October 2005 outbreak of avian epizootic with HPAI/H5N1 was documented and until February 2008 more than 236,000 poultry were killed. Since then the question of monitoring of infected both migrating birds and poultry in places of cross contact in Ukraine remains of high priority. The test system is developed for identification and genotyping A H5N1 on three genes (M, H5 and N1 HPAI/H5N1 in real-time mode for polymerase chain reaction. Test kit capacity to detect HPAI/h5n1avian influenza virus and differentiate it from the other viral infection agents of birds and animals were studied by testing of HPAI/H5N1 virus isolated during mass infection outbreak in Crimea in 2005 and cultural specimens of other viral pathogens. It was established that the «DIA Real Avian Influenza» test kit was capable to detect RNA influenza A virus of high pathogenic H5N1 strains having high sensitivity (100% while RNA of the Crimean HPAI/H5N1 isolate studying and specificity (100% while RNA viruses of Newcastle birds disease, fowl powershift, syndrome of drop in egg production and horse influenza studying.

Eco-Virological Approach for Assessing the Role of Wild Birds in the Spread of Avian Influenza H5N1 along the Central Asian Flyway

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Newman, Scott H.; Hill, Nichola J.; Spragens, Kyle A.; Janies, Daniel; Voronkin, Igor O.; Prosser, Diann J.; Yan, Baoping; Lei, Fumin; Batbayar, Nyambayar; Natsagdorj, Tseveenmyadag; Bishop, Charles M.; Butler, Patrick J.; Wikelski, Martin; Balachandran, Sivananinthaperumal; Mundkur, Taej; Douglas, David C.; Takekawa, John Y.

2012-01-01

A unique pattern of highly pathogenic avian influenza (HPAI) H5N1 outbreaks has emerged along the Central Asia Flyway, where infection of wild birds has been reported with steady frequency since 2005. We assessed the potential for two hosts of HPAI H5N1, the bar-headed goose (Anser indicus) and ruddy shelduck (Tadorna tadorna), to act as agents for virus dispersal along this ‘thoroughfare’. We used an eco-virological approach to compare the migration of 141 birds marked with GPS satellite transmitters during 2005–2010 with: 1) the spatio-temporal patterns of poultry and wild bird outbreaks of HPAI H5N1, and 2) the trajectory of the virus in the outbreak region based on phylogeographic mapping. We found that biweekly utilization distributions (UDs) for 19.2% of bar-headed geese and 46.2% of ruddy shelduck were significantly associated with outbreaks. Ruddy shelduck showed highest correlation with poultry outbreaks owing to their wintering distribution in South Asia, where there is considerable opportunity for HPAI H5N1 spillover from poultry. Both species showed correlation with wild bird outbreaks during the spring migration, suggesting they may be involved in the northward movement of the virus. However, phylogeographic mapping of HPAI H5N1 clades 2.2 and 2.3 did not support dissemination of the virus in a northern direction along the migration corridor. In particular, two subclades (2.2.1 and 2.3.2) moved in a strictly southern direction in contrast to our spatio-temporal analysis of bird migration. Our attempt to reconcile the disciplines of wild bird ecology and HPAI H5N1 virology highlights prospects offered by both approaches as well as their limitations. PMID:22347393

Eco-virological approach for assessing the role of wild birds in the spread of avian influenza H5N1 along the central Asian flyway

Science.gov (United States)

Newman, Scott H.; Hill, Nichola J.; Spragens, Kyle A.; Janies, Daniel; Voronkin, Igor O.; Prosser, Diann J.; Yan, Baoping; Lei, Fumin; Batbayar, Nyambayar; Natsagdorj, Tseveenmyadag; Bishop, Charles M.; Butler, Patrick J.; Wikelski, Martin; Balachandran, Sivananinthaperumal; Mundkur, Taej; Douglas, David C.; Takekawa, John Y.

2012-01-01

A unique pattern of highly pathogenic avian influenza (HPAI) H5N1 outbreaks has emerged along the Central Asia Flyway, where infection of wild birds has been reported with steady frequency since 2005. We assessed the potential for two hosts of HPAI H5N1, the bar-headed goose (Anser indicus) and ruddy shelduck (Tadorna tadorna), to act as agents for virus dispersal along this ‘thoroughfare’. We used an eco-virological approach to compare the migration of 141 birds marked with GPS satellite transmitters during 2005–2010 with: 1) the spatio-temporal patterns of poultry and wild bird outbreaks of HPAI H5N1, and 2) the trajectory of the virus in the outbreak region based on phylogeographic mapping. We found that biweekly utilization distributions (UDs) for 19.2% of bar-headed geese and 46.2% of ruddy shelduck were significantly associated with outbreaks. Ruddy shelduck showed highest correlation with poultry outbreaks owing to their wintering distribution in South Asia, where there is considerable opportunity for HPAI H5N1 spillover from poultry. Both species showed correlation with wild bird outbreaks during the spring migration, suggesting they may be involved in the northward movement of the virus. However, phylogeographic mapping of HPAI H5N1 clades 2.2 and 2.3 did not support dissemination of the virus in a northern direction along the migration corridor. In particular, two subclades (2.2.1 and 2.3.2) moved in a strictly southern direction in contrast to our spatio-temporal analysis of bird migration. Our attempt to reconcile the disciplines of wild bird ecology and HPAI H5N1 virology highlights prospects offered by both approaches as well as their limitations.

The effect of age on the pathogenesis of a highly pathogenic avian influenza (HPAI) H5N1 virus in Pekin ducks (Anas platyrhynchos) infected experimentally

OpenAIRE

L?ndt, Brandon Z.; N??ez, Alejandro.; Banks, Jill; Alexander, Dennis J.; Russell, Christine; Richard? L?ndt, Angela C.; Brown, Ian H.

2009-01-01

Background? Highly pathogenic avian influenza (HPAI) H5N1 viruses have recently displayed increased virulence for wild waterfowl. Objectives? To study the effect of host age on the shedding and tissue dissemination of a HPAI H5N1 virus in infected Pekin ducks. Methods? Pekin ducks in two age?matched groups (n?=?18), 8 and 12?weeks old (wo) were each infected with 106 EID50/0?1?ml of HPAI A/turkey/Turkey/1/05 (H5N1, clade 2?2). Each day for 5?days, birds were monitored clinically, and cloacal ...

Pathogenesis of Highly Pathogenic Avian Influenza (HPAI) A/turkey/Turkey/1/2005 H5N1 in Pekin ducks (Anas platyrhynchos) infected experimentally

OpenAIRE

Löndt , Brandon Z.; Nunez , Alejandro; Banks , Jill; Nili , Hassan; Johnson , Linda K; Alexander , Dennis

2008-01-01

Abstract Asian H5N1 (hereafter referred to as panzootic H5N1) highly pathogenic avian influenza (HPAI) virus has caused large numbers of deaths in both poultry and wild bird populations. Recent isolates of this virus have been reported to cause disease and death in commercial ducks, which has not been seen with other HPAI viruses. However, little is known about the dissemination of this H5N1 within the organs and the cause of death in infected ducks. Nineteen 4-week-old Pekin ducks...

Risk factors associated with highly pathogenic avian influenza subtype H5N8 outbreaks on broiler duck farms in South Korea.

Science.gov (United States)

Kim, W-H; An, J-U; Kim, J; Moon, O-K; Bae, S H; Bender, J B; Cho, S

2018-04-19

Highly Pathogenic Avian Influenza (HPAI) subtype H5N8 outbreaks occurred in poultry farms in South Korea in 2014 resulting in significant damage to the poultry industry. Between 2014 and 2016, the pandemic disease caused significant economic loss and social disruption. To evaluate the risk factors for HPAI infection in broiler duck farms, we conducted a retrospective case-control study on broiler duck farms. Forty-three farms with confirmed laboratories on premises were selected as the case group, and 43 HPAI-negative farms were designated as the control group. Control farms were matched based on farm location and were within a 3-km radius from the case premises. Spatial and environmental factors were characterized by site visit and plotted through a geographic information system (GIS). Univariable and multivariable logistic regression models were developed to assess possible risk factors associated with HPAI broiler duck farm infection. Four final variables were identified as risk factors in a final multivariable logistic model: "Farms with ≥7 flocks" (odds ratio [OR] = 6.99, 95% confidence interval [CI] 1.34-37.04), "Farm owner with ≥15 years of raising poultry career" (OR = 7.91, 95% CI 1.69-37.14), "Presence of any poultry farms located within 500 m of the farm" (OR = 6.30, 95% CI 1.08-36.93) and "Not using a faecal removal service" (OR = 27.78, 95% CI 3.89-198.80). This highlights that the HPAI H5N8 outbreaks in South Korea were associated with farm owner education, number of flocks and facilities and farm biosecurity. Awareness of these factors may help to reduce the spread of HPAI H5N8 across broiler duck farms in Korea during epidemics. Greater understanding of the risk factors for H5N8 may improve farm vulnerability to HPAI and other subtypes and help to establish policies to prevent re-occurrence. These findings are relevant to global prevention recommendations and intervention protocols. © 2018 Blackwell Verlag GmbH.

H7N9 and H5N1 avian influenza suitability models for China: accounting for new poultry and live-poultry markets distribution data.

Science.gov (United States)

Artois, Jean; Lai, Shengjie; Feng, Luzhao; Jiang, Hui; Zhou, Hang; Li, Xiangping; Dhingra, Madhur S; Linard, Catherine; Nicolas, Gaëlle; Xiao, Xiangming; Robinson, Timothy P; Yu, Hongjie; Gilbert, Marius

2017-01-01

In the last two decades, two important avian influenza viruses infecting humans emerged in China, the highly pathogenic avian influenza (HPAI) H5N1 virus in the late nineties, and the low pathogenic avian influenza (LPAI) H7N9 virus in 2013. China is home to the largest population of chickens (4.83 billion) and ducks (0.694 billion), representing, respectively 23.1 and 58.6% of the 2013 world stock, with a significant part of poultry sold through live-poultry markets potentially contributing to the spread of avian influenza viruses. Previous models have looked at factors associated with HPAI H5N1 in poultry and LPAI H7N9 in markets. However, these have not been studied and compared with a consistent set of predictor variables. Significant progress was recently made in the collection of poultry census and live-poultry market data, which are key potential factors in the distribution of both diseases. Here we compiled and reprocessed a new set of poultry census data and used these to analyse HPAI H5N1 and LPAI H7N9 distributions with boosted regression trees models. We found a limited impact of the improved poultry layers compared to models based on previous poultry census data, and a positive and previously unreported association between HPAI H5N1 outbreaks and the density of live-poultry markets. In addition, the models fitted for the HPAI H5N1 and LPAI H7N9 viruses predict a high risk of disease presence for the area around Shanghai and Hong Kong. The main difference in prediction between the two viruses concerned the suitability of HPAI H5N1 in north-China around the Yellow sea (outlined with Tianjin, Beijing, and Shenyang city) where LPAI H7N9 has not spread intensely.

Anthropogenic factors and the risk of highly pathogenic avian influenza H5N1: prospects from a spatial-based model.

Science.gov (United States)

Paul, Mathilde; Tavornpanich, Saraya; Abrial, David; Gasqui, Patrick; Charras-Garrido, Myriam; Thanapongtharm, Weerapong; Xiao, Xiangming; Gilbert, Marius; Roger, Francois; Ducrot, Christian

2010-01-01

Beginning in 2003, highly pathogenic avian influenza (HPAI) H5N1 virus spread across Southeast Asia, causing unprecedented epidemics. Thailand was massively infected in 2004 and 2005 and continues today to experience sporadic outbreaks. While research findings suggest that the spread of HPAI H5N1 is influenced primarily by trade patterns, identifying the anthropogenic risk factors involved remains a challenge. In this study, we investigated which anthropogenic factors played a role in the risk of HPAI in Thailand using outbreak data from the "second wave" of the epidemic (3 July 2004 to 5 May 2005) in the country. We first performed a spatial analysis of the relative risk of HPAI H5N1 at the subdistrict level based on a hierarchical Bayesian model. We observed a strong spatial heterogeneity of the relative risk. We then tested a set of potential risk factors in a multivariable linear model. The results confirmed the role of free-grazing ducks and rice-cropping intensity but showed a weak association with fighting cock density. The results also revealed a set of anthropogenic factors significantly linked with the risk of HPAI. High risk was associated strongly with densely populated areas, short distances to a highway junction, and short distances to large cities. These findings highlight a new explanatory pattern for the risk of HPAI and indicate that, in addition to agro-environmental factors, anthropogenic factors play an important role in the spread of H5N1. To limit the spread of future outbreaks, efforts to control the movement of poultry products must be sustained. INRA, EDP Sciences, 2010.

Experimental infection of clade 1.1.2 (H5N1), clade 2.3.2.1c (H5N1) and clade 2.3.4.4 (H5N6) highly pathogenic avian influenza viruses in dogs.

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Lyoo, K S; Na, W; Phan, L V; Yoon, S W; Yeom, M; Song, D; Jeong, D G

2017-12-01

Since the emergence of highly pathogenic avian influenza (HPAI) H5N1 in Asia, the haemagglutinin (HA) gene of this virus lineage has continued to evolve in avian populations, and H5N1 lineage viruses now circulate concurrently worldwide. Dogs may act as an intermediate host, increasing the potential for zoonotic transmission of influenza viruses. Virus transmission and pathologic changes in HPAI clade 1.1.2 (H5N1)-, 2.3.2.1c (H5N1)- and 2.3.4.4 (H5N6)-infected dogs were investigated. Mild respiratory signs and antibody response were shown in dogs intranasally infected with the viruses. Lung histopathology showed lesions that were associated with moderate interstitial pneumonia in the infected dogs. In this study, HPAI H5N6 virus replication in dogs was demonstrated for the first time. Dogs have been suspected as a "mixing vessel" for reassortments between avian and human influenza viruses to occur. The replication of these three subtypes of the H5 lineage of HPAI viruses in dogs suggests that dogs could serve as intermediate hosts for avian-human influenza virus reassortment if they are also co-infected with human influenza viruses. © 2017 Blackwell Verlag GmbH.

Seasonal patterns in human A (H5N1 virus infection: analysis of global cases.

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Maya B Mathur

Full Text Available Human cases of highly pathogenic avian influenza (HPAI A (H5N1 have high mortality. Despite abundant data on seasonal patterns in influenza epidemics, it is unknown whether similar patterns exist for human HPAI H5N1 cases worldwide. Such knowledge could help decrease avian-to-human transmission through increased prevention and control activities during peak periods.We performed a systematic search of published human HPAI H5N1 cases to date, collecting month, year, country, season, hemisphere, and climate data. We used negative binomial regression to predict changes in case incidence as a function of season. To investigate hemisphere as a potential moderator, we used AIC and the likelihood-ratio test to compare the season-only model to nested models including a main effect or interaction with hemisphere. Finally, we visually assessed replication of seasonal patterns across climate groups based on the Köppen-Geiger climate classification.We identified 617 human cases (611 with complete seasonal data occurring in 15 countries in Southeast Asia, Africa, and the Middle East. Case occurrence was much higher in winter (n = 285, p = 0.03 than summer (n = 64, and the winter peak occurred across diverse climate groups. There was no significant interaction between hemisphere and season.Across diverse climates, HPAI H5N1 virus infection in humans increases significantly in winter. This is consistent with increased poultry outbreaks and HPAI H5N1 virus transmission during cold and dry conditions. Prioritizing prevention and control activities among poultry and focusing public health messaging to reduce poultry exposures during winter months may help to reduce zoonotic transmission of HPAI H5N1 virus in resource-limited settings.

High-yield production of a stable Vero cell-based vaccine candidate against the highly pathogenic avian influenza virus H5N1

International Nuclear Information System (INIS)

Zhou, Fangye; Zhou, Jian; Ma, Lei; Song, Shaohui; Zhang, Xinwen; Li, Weidong; Jiang, Shude; Wang, Yue; Liao, Guoyang

2012-01-01

Highlights: ► Vero cell-based HPAI H5N1 vaccine with stable high yield. ► Stable high yield derived from the YNVa H3N2 backbone. ► H5N1/YNVa has a similar safety and immunogenicity to H5N1delta. -- Abstract: Highly pathogenic avian influenza (HPAI) viruses pose a global pandemic threat, for which rapid large-scale vaccine production technology is critical for prevention and control. Because chickens are highly susceptible to HPAI viruses, the supply of chicken embryos for vaccine production might be depleted during a virus outbreak. Therefore, developing HPAI virus vaccines using other technologies is critical. Meeting vaccine demand using the Vero cell-based fermentation process has been hindered by low stability and yield. In this study, a Vero cell-based HPAI H5N1 vaccine candidate (H5N1/YNVa) with stable high yield was achieved by reassortment of the Vero-adapted (Va) high growth A/Yunnan/1/2005(H3N2) (YNVa) virus with the A/Anhui/1/2005(H5N1) attenuated influenza vaccine strain (H5N1delta) using the 6/2 method. The reassorted H5N1/YNVa vaccine maintained a high hemagglutination (HA) titer of 1024. Furthermore, H5N1/YNVa displayed low pathogenicity and uniform immunogenicity compared to that of the parent virus.

Military and Military Medical Support in Highly Pathogenic Avian Influenza (HPAI/H5N1) Pandemic Scenario

International Nuclear Information System (INIS)

Taleski, V.

2007-01-01

Avian influenza (Bird flu) is a highly contagious viral disease affecting mainly chickens, turkeys, ducks, other birds and mammals. Reservoirs for HPAI /H5N1 virus are shore birds and waterfowl (asymptomatic, excrete virus in feces for a long periods of time), live bird markets and commercial swine facilities. Virus tends to cycle between pigs and birds. HPAI (H5N1) virus is on every 'top ten' list available for potential agricultural bio-weapon agents. The threat of a HPAI/H5N1 pandemic is a definitively global phenomenon and the response must be global. A number of National plans led to various measures of preventing and dealing with epidemics/pandemics. Lessons learned form the pandemic history indicated essential role of military and military medical support to civil authorities in a crisis situation. Based on International Military Medical Avian Influenza Pandemic workshop (Vienna 2006), an expected scenario would involve 30-50% outpatients, 20-30% hospital admission, 2-3% deaths, 10-20% complicated cases. Activities of civil hospital may be reduced by 50%. Benefits of military support could be in: Transportation of patients (primarily by air); Mass vaccination and provision of all other preventive measures (masks, Tamiflu); Restriction of movements; Infection control of health care facilities; Field hospitals for triage and quarantine, military barracks to treat milder cases and military hospitals for severe cases; Deal with corpses; Stockpiling (vaccines, antiviral, antibiotics, protective equipment, supplies); Training; Laboratories; Ensure public safety, etc. With the aim of minimizing the risk of a pandemic spread by means of rapid and uncomplicated cooperation, an early warning system has to be established to improve surveillance, improve international contacts (WHO, ECDC, CDC), establish Platform for sharing information, close contacts of national and international military and civilian surveillance networks and databases, cooperation between military

High-yield production of a stable Vero cell-based vaccine candidate against the highly pathogenic avian influenza virus H5N1

Energy Technology Data Exchange (ETDEWEB)

Zhou, Fangye; Zhou, Jian; Ma, Lei; Song, Shaohui; Zhang, Xinwen; Li, Weidong; Jiang, Shude [No. 5, Department of Bioproducts, Institute of Medical Biology, Chinese Academy of Medical Science and Pecking Union Medical College, Jiaoling Avenue 935, Kunming, Yunnan Province 650102, People' s Republic of China (China); Wang, Yue [National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Yingxin Lane 100, Xicheng District, Beijing 100052, People' s Republic of China (China); Liao, Guoyang [No. 5, Department of Bioproducts, Institute of Medical Biology, Chinese Academy of Medical Science and Pecking Union Medical College, Jiaoling Avenue 935, Kunming, Yunnan Province 650102, People' s Republic of China (China)

2012-05-18

Highlights: Black-Right-Pointing-Pointer Vero cell-based HPAI H5N1 vaccine with stable high yield. Black-Right-Pointing-Pointer Stable high yield derived from the YNVa H3N2 backbone. Black-Right-Pointing-Pointer H5N1/YNVa has a similar safety and immunogenicity to H5N1delta. -- Abstract: Highly pathogenic avian influenza (HPAI) viruses pose a global pandemic threat, for which rapid large-scale vaccine production technology is critical for prevention and control. Because chickens are highly susceptible to HPAI viruses, the supply of chicken embryos for vaccine production might be depleted during a virus outbreak. Therefore, developing HPAI virus vaccines using other technologies is critical. Meeting vaccine demand using the Vero cell-based fermentation process has been hindered by low stability and yield. In this study, a Vero cell-based HPAI H5N1 vaccine candidate (H5N1/YNVa) with stable high yield was achieved by reassortment of the Vero-adapted (Va) high growth A/Yunnan/1/2005(H3N2) (YNVa) virus with the A/Anhui/1/2005(H5N1) attenuated influenza vaccine strain (H5N1delta) using the 6/2 method. The reassorted H5N1/YNVa vaccine maintained a high hemagglutination (HA) titer of 1024. Furthermore, H5N1/YNVa displayed low pathogenicity and uniform immunogenicity compared to that of the parent virus.

National surveillance and control costs for highly pathogenic avian influenza H5N1 in poultry: A benefit-cost assessment for a developing economy, Nigeria.

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Fasanmi, Olubunmi G; Kehinde, Olugbenga O; Laleye, Agnes T; Ekong, Bassey; Ahmed, Syed S U; Fasina, Folorunso O

2018-06-13

We conducted benefit-cost analysis of outbreak and surveillance costs for HPAI H5N1in poultry in Nigeria. Poultry's death directly cost US$ 939,734.0 due to outbreaks. The integrated disease surveillance and response originally created for comprehensive surveillance and laboratory investigation of human diseases was adapted for HPAI H5N1 in poultry. Input data were obtained from the field, government documents and repositories and peer-reviewed publications. Actual/forecasted bird numbers lost were integrated into a financial model and estimates of losses were calculated. Costs of surveillance as alternative intervention were determined based on previous outbreak control costs and outputs were generated in SurvCost® with sensitivity analyses for different scenarios. Uncontrolled outbreaks will lead to loss of over US$ 2.2 billion annually in Nigeria with 47.8% of the losses coming from eggs. The annual cost of all animal related health activities was cost was 96.2% of the total surveillance and response costs, and 31.0% of the HPAI surveillance cost was spent on personnel with 3.8% as capital cost. Cost-wisely, routine monitoring and surveillance for HPAI are 68 times more cost effective than to do nothing. Assuming that successful control and eradication of HPAI H5N1 is partially attributable to H5N1 surveillance and response, a quarter or half of the success will result in 17 or 34 times more benefits. Although animal surveillance and response activities for avian influenza appeared expensive, their implementation are economically cost beneficial for developing countries. Copyright © 2018 Elsevier Ltd. All rights reserved.

Efficacy of single dose of a bivalent vaccine containing inactivated Newcastle disease virus and reassortant highly pathogenic avian influenza H5N1 virus against lethal HPAI and NDV infection in chickens.

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Dong-Hun Lee

Full Text Available Highly pathogenic avian influenza (HPAI and Newcastle disease (ND are 2 devastating diseases of poultry, which cause great economic losses to the poultry industry. In the present study, we developed a bivalent vaccine containing antigens of inactivated ND and reassortant HPAI H5N1 viruses as a candidate poultry vaccine, and we evaluated its immunogenicity and protective efficacy in specific pathogen-free chickens. The 6:2 reassortant H5N1 vaccine strain containing the surface genes of the A/Chicken/Korea/ES/2003(H5N1 virus was successfully generated by reverse genetics. A polybasic cleavage site of the hemagglutinin segment was replaced by a monobasic cleavage site. We characterized the reverse genetics-derived reassortant HPAI H5N1 clade 2.5 vaccine strain by evaluating its growth kinetics in eggs, minimum effective dose in chickens, and cross-clade immunogenicity against HPAI clade 1 and 2. The bivalent vaccine was prepared by emulsifying inactivated ND (La Sota strain and reassortant HPAI viruses with Montanide ISA 70 adjuvant. A single immunization with this vaccine induced high levels of hemagglutination-inhibiting antibody titers and protected chickens against a lethal challenge with the wild-type HPAI and ND viruses. Our results demonstrate that the bivalent, inactivated vaccine developed in this study is a promising approach for the control of both HPAI H5N1 and ND viral infections.

The pathogenecity of H5N1 highly pathogenic Avian Influenza (HPAI virus clade 2.3.2. in Indonesian indigenous chicken by contact tranmission with infected duck

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R. Damayanti

2017-05-01

Full Text Available An experimental transmission study was conducted using nine healthy Indonesian indigenous chickens placed together with two 30 days old ducks which were experimentally infected with H5N1 HPAI clade 2.3.2 virus in the Biosafety Laboratory Level 3 (BSL-3 facilities. The aim of the study was to find out the pathogenicity of H5N1 HPAI virus clade 2.3.2 in Indonesian indigenous chickens. The study showed that within twenty four hours rearing, the chickens were exhibited mild clinical signs and by 48 hours, all of the chickens died, whereas the ducks survived but with severe clinical signs. The H5N1 HPAI virus has been successfully isolated from chickens and ducks swabs, confirming that those animals were infected by the virus. Histologically, the infected chicken encountered with severe inflammation reaction namely non suppuratives encephalitis, tracheitis, myocarditis, interstitial pneumonia, hepatitis, proventriculitis, enteritis, pancreatitis, nephritis and bursitis. Necrotizing spleen and pancreas were also prominent. Viral antigen was detected by immunohistochemistry staining in various affected visceral organs. This suggests that Indonesian indigenous chickens were susceptible to H5N1 HPAI virus clade 2.3.2 and it can be transmitted easily to Indonesian indigenous chickens by contact transmission with infected ducks.

The effect of age on the pathogenesis of a highly pathogenic avian influenza (HPAI) H5N1 virus in Pekin ducks (Anas platyrhynchos) infected experimentally.

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Löndt, Brandon Z; Núñez, Alejandro; Banks, Jill; Alexander, Dennis J; Russell, Christine; Richard-Löndt, Angela C; Brown, Ian H

2010-01-01

Highly pathogenic avian influenza (HPAI) H5N1 viruses have recently displayed increased virulence for wild waterfowl. To study the effect of host age on the shedding and tissue dissemination of a HPAI H5N1 virus in infected Pekin ducks. Pekin ducks in two age-matched groups (n = 18), 8 and 12 weeks old (wo) were each infected with 10(6) EID(50)/0.1 ml of HPAI A/turkey/Turkey/1/05 (H5N1, clade 2.2). Each day for 5 days, birds were monitored clinically, and cloacal and oropharyngeal swabs collected, before three birds from each group were selected randomly for post-mortem examination. Tissue samples were collected for examination by real-time RT-PCR, histopathology and immunohistochemistry (IHC). Severe clinical signs, including incoordination and torticollis were observed in the 8 wo group resulting in 100% mortality by 4 dpi. Mild clinical signs were observed in the 12 wo group with no mortality. Real-time RT-PCR and IHC results demonstrated the systemic spread of H5N1 virus in birds of both age groups. Higher levels of virus shedding were detected in oropharyngeal swabs than in cloacal swabs, with similar levels of shedding detected in both age groups. Variations in level and temporal dissemination of virus within tissues of older ducks, and the presence of the virus in brain and heart were observed, which coincided with the appearance of clinical signs preceding death in younger birds. These results are consistent with reports of natural infections of wild waterfowl and poultry possibly indicating an age-related association with dissemination and clinical outcome in ducks following infection with H5N1 HPAI virus.

Isolation and identification of highly pathogenic avian influenza virus subtype H5N1 in peafowl (Pavo cristatus).

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Ismail, Mahmoud Moussa; Khan, Owais Ahmed; Cattoli, Giovanni; Lu, Huaguang

2010-03-01

An outbreak of highly pathogenic avian influenza (HPAI) virus subtype H5N1 was first diagnosed in a "backyard" flock of peafowl (Pavo cristatus) raised on palace premises in the Kingdom of Saudi Arabia in December 3, 2007. The flock consisted of 40 peafowl, and their ages ranged from 3 to 5 years old. Affected birds suffered from depression, anorexia, and white diarrhea. Four dead birds were submitted for HPAI diagnosis at the Central Veterinary Diagnostic Laboratory in Riyadh. Brain and liver tissues and tracheal and cloacal swabs were taken from the dead birds and processed for a real-time reverse transcriptase (RT)-PCR test and virus isolation in specific-pathogen-free embryonating chicken eggs. The H5N1 subtype of avian influenza virus was isolated from the four dead birds and identified by a real-time RT-PCR before and after egg inoculation. The virus isolates were characterized as HPAI H5N1 virus by sequencing analysis. Phylogenetic comparisons revealed that the H5N1 viruses isolated from peafowl belong to the genetic clade 2.2 according to the World Health Organization nomenclature. The peafowl H5N1 virus falls into 2.2.2 sublineage II and clusters with the H5N1 viruses isolated from poultry in Saudi Arabia in 2007-08.

Multivalent HA DNA vaccination protects against highly pathogenic H5N1 avian influenza infection in chickens and mice.

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Srinivas Rao

Full Text Available Sustained outbreaks of highly pathogenic avian influenza (HPAI H5N1 in avian species increase the risk of reassortment and adaptation to humans. The ability to contain its spread in chickens would reduce this threat and help maintain the capacity for egg-based vaccine production. While vaccines offer the potential to control avian disease, a major concern of current vaccines is their potency and inability to protect against evolving avian influenza viruses.The ability of DNA vaccines encoding hemagglutinin (HA proteins from different HPAI H5N1 serotypes was evaluated for its ability to elicit neutralizing antibodies and to protect against homologous and heterologous HPAI H5N1 strain challenge in mice and chickens after DNA immunization by needle and syringe or with a pressure injection device. These vaccines elicited antibodies that neutralized multiple strains of HPAI H5N1 when given in combinations containing up to 10 HAs. The response was dose-dependent, and breadth was determined by the choice of the influenza virus HA in the vaccine. Monovalent and trivalent HA vaccines were tested first in mice and conferred protection against lethal H5N1 A/Vietnam/1203/2004 challenge 68 weeks after vaccination. In chickens, protection was observed against heterologous strains of HPAI H5N1 after vaccination with a trivalent H5 serotype DNA vaccine with doses as low as 5 microg DNA given twice either by intramuscular needle injection or with a needle-free device.DNA vaccines offer a generic approach to influenza virus immunization applicable to multiple animal species. In addition, the ability to substitute plasmids encoding different strains enables rapid adaptation of the vaccine to newly evolving field isolates.

Defining "Sector 3" Poultry Layer Farms in Relation to H5N1-HPAI-An Example from Java, Indonesia.

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Durr, Peter A; Wibowo, Michael Haryadi; Tarigan, Simson; Artanto, Sidna; Rosyid, Murni Nurhasanah; Ignjatovic, Jagoda

2016-05-01

To help guide surveillance and control of highly pathogenic avian influenza subtype H5N1 (H5N1-HPAI), the Food and Agriculture Organization of the United Nations in 2004 devised a poultry farm classification system based on a combination of production and biosecurity practices. Four "Sectors" were defined, and this scheme has been widely adopted within Indonesia to guide national surveillance and control strategies. Nevertheless, little detailed research into the robustness of this classification system has been conducted, particularly as it relates to independent, small to medium-sized commercial poultry farms (Sector 3). Through an analysis of questionnaire data collected as part of a survey of layer farms in western and central Java, all of which were classified as Sector 3 by local veterinarians, we provide benchmark data on what defines this sector. A multivariate analysis of the dataset, using hierarchical cluster analysis, identified three groupings of the farms, which were defined by a combination of production-and biosecurity-related variables, particularly those related to farm size and (the lack of) washing and disinfection practices. Nevertheless, the relationship between production-related variables and positive biosecurity practices was poor, and larger farms did not have an overall higher total biosecurity score than small or medium-sized ones. Further research is required to define the properties of poultry farms in Indonesia that are most closely related to effective biosecurity and the prevention of H5N1-HPAI.

Reduced experimental infectivity and transmissibility of intercontinental H5 (H5N8 and H5N2) compared to Eurasian H5N1 highly pathogenic avian influenza viruses for chickens, turkeys, and Japanese quail

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H5N1 high pathogenicity avian influenza (HPAI) virus (HPAIV) emerged in 1996 in Guangdong China and has since spread to infect and cause deaths in wild birds, poultry and humans in over 63 countries in Asia, Europe and Africa; and more recently a reassortant H5N8 clade 2.3.4.4 HPAI virus has spread ...

Infection of mice with a human influenza A/H3N2 virus induces protective immunity against lethal infection with influenza A/H5N1 virus.

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Kreijtz, J H C M; Bodewes, R; van den Brand, J M A; de Mutsert, G; Baas, C; van Amerongen, G; Fouchier, R A M; Osterhaus, A D M E; Rimmelzwaan, G F

2009-08-06

The transmission of highly pathogenic avian influenza (HPAI) A viruses of the H5N1 subtype from poultry to man and the high case fatality rate fuels the fear for a pandemic outbreak caused by these viruses. However, prior infections with seasonal influenza A/H1N1 and A/H3N2 viruses induce heterosubtypic immunity that could afford a certain degree of protection against infection with the HPAI A/H5N1 viruses, which are distantly related to the human influenza A viruses. To assess the protective efficacy of such heterosubtypic immunity mice were infected with human influenza virus A/Hong Kong/2/68 (H3N2) 4 weeks prior to a lethal infection with HPAI virus A/Indonesia/5/05 (H5N1). Prior infection with influenza virus A/Hong Kong/2/68 reduced clinical signs, body weight loss, mortality and virus replication in the lungs as compared to naive mice infected with HPAI virus A/Indonesia/5/05. Priming by infection with respiratory syncytial virus, a non-related virus did not have a beneficial effect on the outcome of A/H5N1 infections, indicating that adaptive immune responses were responsible for the protective effect. In mice primed by infection with influenza A/H3N2 virus cytotoxic T lymphocytes (CTL) specific for NP(366-374) epitope ASNENMDAM and PA(224-232) SCLENFRAYV were observed. A small proportion of these CTL was cross-reactive with the peptide variant derived from the influenza A/H5N1 virus (ASNENMEVM and SSLENFRAYV respectively) and upon challenge infection with the influenza A/H5N1 virus cross-reactive CTL were selectively expanded. These CTL, in addition to those directed to conserved epitopes, shared by the influenza A/H3N2 and A/H5N1 viruses, most likely contributed to accelerated clearance of the influenza A/H5N1 virus infection. Although also other arms of the adaptive immune response may contribute to heterosubtypic immunity, the induction of virus-specific CTL may be an attractive target for development of broad protective vaccines. Furthermore the

Recognizing true H5N1 infections in humans during confirmed outbreaks.

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Zaman, Mukhtiar; Gasimov, Viktor; Oner, Ahmet Faik; Dogan, Nazim; Adisasmito, Wiku; Coker, Richard; Bamgboye, Ebun L; Chan, Paul K S; Hanshaoworakul, Wanna; Lee, Nelson; Phommasack, Bounlay; Touch, Sok; Tsang, Owen; Swenson, Anna; Toovey, Stephen; Dreyer, Nancy Ann

2014-02-13

The goal of this study was to evaluate whether any characteristics that are evident at presentation for urgent medical attention could be used to differentiate cases of H5N1 in the absence of viral testing. Information about exposure to poultry, clinical signs and symptoms, treatments, and outcomes was abstracted from existing data in the global avian influenza registry (www.avianfluregistry.org) using standardized data collection tools for documented and possible cases of H5N1 infection who presented for medical attention between 2005-2011 during known H5N1 outbreaks in Azerbaijan, Indonesia, Pakistan and Turkey. Demography, exposure to poultry, and presenting symptoms were compared, with only the common symptoms of fever and headache presenting significantly more frequently in confirmed H5N1 cases than in possible cases. Reported exposure to  infected humans was also more common in confirmed cases. In contrast, unexplained respiratory illness, sore throat, excess sputum production, and rhinorrhea were more frequent in possible cases. Overall, oseltamivir treatment showed a survival benefit, with the greatest benefit shown in H5N1 cases who were treated within two days of symptom onset (51% reduction in case fatality). Since prompt treatment with antivirals conferred a strong survival benefit for H5N1 cases, presumptive antiviral treatment should be considered for all possible cases presenting during an outbreak of H5N1 as a potentially life-saving measure.

Migratory Whooper Swans Cygnus cygnus Transmit H5N1 Virus between China and Mongolia: Combination Evidence from Satellite Tracking and Phylogenetics Analysis.

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Li, Shuhong; Meng, Weiyue; Liu, Dongping; Yang, Qiqi; Chen, Lixia; Dai, Qiang; Ma, Tian; Gao, Ruyi; Ru, Wendong; Li, Yunfeng; Yu, Pengbo; Lu, Jun; Zhang, Guogang; Tian, Huaiyu; Chai, Hongliang; Li, Yanbing

2018-05-04

In late 2014, a highly pathogenic avian influenza (hereafter HPAI) H5N1 outbreak infected whooper swans Cygnus cygnus wintering at the Sanmenxia Reservoir area, China, and raised concerns about migratory linkages between wintering and breeding grounds of whooper swans. In this study, 61 swans were satellite tracked from 2013 to 2016 to determine the spatial association of their migration routes and H5N1 outbreaks, and 3596 fecal samples were collected along the migration routes for virology testing. Swans departed the wintering grounds and migrated along the Yellow River, and flew over the Yin Mountains in China. The Brownian bridge movement model showed there was a high degree of spatiotemporal overlap between the core use area along the spring migration pathway and historical H5N1 events in China and Mongolia from 2005 to 2015. The H5N1 strain was isolated and phylogenetic analyses confirmed that the HA gene sequence generated is genetically similar to that of the epidemic strain at a previous wintering site (the Sanmenxia Reservoir area) along its flyway. Our results identified a previously unknown migratory link of whooper swans in central China with Mongolia and confirmed that the swans could carry the HPAI H5N1 virus during migration, resulting in long-distance transmission.

Spatio-temporal dynamics of global H5N1 outbreaks match bird migration patterns

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Yali Si

2009-11-01

Full Text Available The global spread of highly pathogenic avian influenza H5N1 in poultry, wild birds and humans, poses a significant pandemic threat and a serious public health risk. An efficient surveillance and disease control system relies on the understanding of the dispersion patterns and spreading mechanisms of the virus. A space-time cluster analysis of H5N1 outbreaks was used to identify spatio-temporal patterns at a global scale and over an extended period of time. Potential mechanisms explaining the spread of the H5N1 virus, and the role of wild birds, were analyzed. Between December 2003 and December 2006, three global epidemic phases of H5N1 influenza were identified. These H5N1 outbreaks showed a clear seasonal pattern, with a high density of outbreaks in winter and early spring (i.e., October to March. In phase I and II only the East Asia Australian flyway was affected. During phase III, the H5N1 viruses started to appear in four other flyways: the Central Asian flyway, the Black Sea Mediterranean flyway, the East Atlantic flyway and the East Africa West Asian flyway. Six disease cluster patterns along these flyways were found to be associated with the seasonal migration of wild birds. The spread of the H5N1 virus, as demonstrated by the space-time clusters, was associated with the patterns of migration of wild birds. Wild birds may therefore play an important role in the spread of H5N1 over long distances. Disease clusters were also detected at sites where wild birds are known to overwinter and at times when migratory birds were present. This leads to the suggestion that wild birds may also be involved in spreading the H5N1 virus over short distances.

Overview of incursions of Asian H5N1 subtype highly pathogenic avian influenza virus into Great Britain, 2005-2008.

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Alexander, Dennis J; Manvell, Ruth J; Irvine, Richard; Londt, Brandon Z; Cox, Bill; Ceeraz, Vanessa; Banks, Jill; Browna, Ian H

2010-03-01

Since 2005 there have been five incursions into Great Britain of highly pathogenic avian influenza (HPAI) viruses of subtype H5N1 related to the ongoing global epizootic. The first incursion occurred in October 2005 in birds held in quarantine after importation from Taiwan. Two incursions related to wild birds: one involved a single dead whooper swan found in March 2006 in the sea off the east coast of Scotland, and the other involved 10 mute swans and a Canada goose found dead over the period extending from late December 2007 to late February 2008 on or close to a swannery on the south coast of England. The other two outbreaks occurred in commercial poultry in January 2007 and November 2007, both in the county of Suffolk. The first of these poultry outbreaks occurred on a large turkey farm, and there was no further spread. The second outbreak occurred on a free-range farm rearing turkeys, ducks, and geese and spread to birds on a second turkey farm that was culled as a dangerous contact. Viruses isolated from these five outbreaks were confirmed to be Asian H5N1 HPAI viruses; the quarantine outbreak was attributed to a clade 2.3 virus and the other four to clade 2.2 viruses. This article describes the outbreaks, their control, and the possible origins of the responsible viruses.

Comparison of human and animal surveillance data for H5N1 influenza A in Egypt 2006-2011.

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Peter M Rabinowitz

Full Text Available BACKGROUND: The majority of emerging infectious diseases are zoonotic (transmissible between animals and humans in origin, and therefore integrated surveillance of disease events in humans and animals has been recommended to support effective global response to disease emergence. While in the past decade there has been extensive global surveillance for highly pathogenic avian influenza (HPAI infection in both animals and humans, there have been few attempts to compare these data streams and evaluate the utility of such integration. METHODOLOGY: We compared reports of bird outbreaks of HPAI H5N1 in Egypt for 2006-2011 compiled by the World Organisation for Animal Health (OIE and the UN Food and Agriculture Organization (FAO EMPRESi reporting system with confirmed human H5N1 cases reported to the World Health Organization (WHO for Egypt during the same time period. PRINCIPAL FINDINGS: Both human cases and bird outbreaks showed a cyclic pattern for the country as a whole, and there was a statistically significant temporal correlation between the data streams. At the governorate level, the first outbreak in birds in a season usually but not always preceded the first human case, and the time lag between events varied widely, suggesting regional differences in zoonotic risk and/or surveillance effectiveness. In a multivariate risk model, lower temperature, lower urbanization, higher poultry density, and the recent occurrence of a bird outbreak were associated with increased risk of a human case of HPAI in the same governorate, although the positive predictive value of a bird outbreak was low. CONCLUSIONS: Integrating data streams of surveillance for human and animal cases of zoonotic disease holds promise for better prediction of disease risk and identification of environmental and regional factors that can affect risk. Such efforts can also point out gaps in human and animal surveillance systems and generate hypotheses regarding disease transmission.

Persistence of highly pathogenic avian influenza H5N1 virus defined by agro-ecological niche

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Hogerwerf, Lenny; Wallace, Rob G.; Ottaviani, Daniela; Slingenbergh, Jan; Prosser, Diann; Bergmann, Luc; Gilbert, Marius

2010-01-01

The highly pathogenic avian influenza (HPAI) H5N1 virus has spread across Eurasia and into Africa. Its persistence in a number of countries continues to disrupt poultry production, impairs smallholder livelihoods, and raises the risk a genotype adapted to human-to-human transmission may emerge. While previous studies identified domestic duck reservoirs as a primary risk factor associated with HPAI H5N1 persistence in poultry in Southeast Asia, little is known of such factors in countries with different agro-ecological conditions, and no study has investigated the impact of such conditions on HPAI H5N1 epidemiology at the global scale. This study explores the patterns of HPAI H5N1 persistence worldwide, and for China, Indonesia, and India includes individual provinces that have reported HPAI H5N1 presence during the 2004–2008 period. Multivariate analysis of a set of 14 agricultural, environmental, climatic, and socio-economic factors demonstrates in quantitative terms that a combination of six variables discriminates the areas with human cases and persistence: agricultural population density, duck density, duck by chicken density, chicken density, the product of agricultural population density and chicken output/input ratio, and purchasing power per capita. The analysis identifies five agro-ecological clusters, or niches, representing varying degrees of disease persistence. The agro-ecological distances of all study areas to the medoid of the niche with the greatest number of human cases are used to map HPAI H5N1 risk globally. The results indicate that few countries remain where HPAI H5N1 would likely persist should it be introduced.

Pathogenicity and Transmission of H5 and H7 Highly Pathogenic Avian Influenza Viruses in Mallards

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Costa-Hurtado, Mar; Shepherd, Eric; DeJesus, Eric; Smith, Diane; Spackman, Erica; Kapczynski, Darrell R.; Suarez, David L.; Stallknecht, David E.; Swayne, David E.

2016-01-01

ABSTRACT Wild aquatic birds have been associated with the intercontinental spread of H5 subtype highly pathogenic avian influenza (HPAI) viruses of the A/goose/Guangdong/1/96 (Gs/GD) lineage during 2005, 2010, and 2014, but dispersion by wild waterfowl has not been implicated with spread of other HPAI viruses. To better understand why Gs/GD H5 HPAI viruses infect and transmit more efficiently in waterfowl than other HPAI viruses, groups of mallard ducks were challenged with one of 14 different H5 and H7 HPAI viruses, including a Gs/GD lineage H5N1 (clade 2.2) virus from Mongolia, part of the 2005 dispersion, and the H5N8 and H5N2 index HPAI viruses (clade 2.3.4.4) from the United States, part of the 2014 dispersion. All virus-inoculated ducks and contact exposed ducks became infected and shed moderate to high titers of the viruses, with the exception that mallards were resistant to Ck/Pennsylvania/83 and Ck/Queretaro/95 H5N2 HPAI virus infection. Clinical signs were only observed in ducks challenged with the H5N1 2005 virus, which all died, and with the H5N8 and H5N2 2014 viruses, which had decreased weight gain and fever. These three viruses were also shed in higher titers by the ducks, which could facilitate virus transmission and spread. This study highlights the possible role of wild waterfowl in the spread of HPAI viruses. IMPORTANCE The spread of H5 subtype highly pathogenic avian influenza (HPAI) viruses of the Gs/GD lineage by migratory waterfowl is a serious concern for animal and public health. H5 and H7 HPAI viruses are considered to be adapted to gallinaceous species (chickens, turkeys, quail, etc.) and less likely to infect and transmit in wild ducks. In order to understand why this is different with certain Gs/GD lineage H5 HPAI viruses, we compared the pathogenicity and transmission of several H5 and H7 HPAI viruses from previous poultry outbreaks to Gs/GD lineage H5 viruses, including H5N1 (clade 2.2), H5N8 and H5N2 (clade 2.3.4.4) viruses, in

H5N2 Highly Pathogenic Avian Influenza Viruses from the US 2014-2015 outbreak have an unusually long pre-clinical period in turkeys

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Spackman, Erica; Pantin-Jackwood, Mary J.; Kapczynski, Darrell R.; Swayne, David E.; Suarez, David L.

2016-01-01

Background From December 2014 through June 2015, the US experienced the most costly highly pathogenic avian influenza (HPAI) outbreak to date. Most cases in commercial poultry were caused by an H5N2 strain which was a reassortant with 5 Eurasian lineage genes, including a clade 2.3.4.4 goose/Guangdong/1996 lineage hemagglutinin, and 3 genes from North American wild waterfowl low pathogenicity avian influenza viruses. The outbreak primarily affected turkeys and table-egg layer type chickens. T...

Efficacy of a Recombinant Turkey Herpesvirus H5 Vaccine Against Challenge With H5N1 Clades 1.1.2 and 2.3.2.1 Highly Pathogenic Avian Influenza Viruses in Domestic Ducks (Anas platyrhynchos domesticus).

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Pantin-Jackwood, Mary J; Kapczynski, Darrell R; DeJesus, Eric; Costa-Hurtado, Mar; Dauphin, Gwenaelle; Tripodi, Astrid; Dunn, John R; Swayne, David E

2016-03-01

Domestic ducks are the second most abundant poultry species in many Asian countries and have played a critical role in the epizootiology of H5N1 highly pathogenic avian influenza (HPAI).In this study, the protective efficacy of a live recombinant vector vaccine based on a turkey herpesvirus (HVT) expressing the H5 gene from a clade 2.2 H5N1 HPAI strain (A/Swan/Hungary/4999/ 2006) (rHVT-H5/2.2), given at 3 days of age, was examined in Pekin ducks (Anas platyrhynchos domesticus). The vaccine was given alone or in combination with an inactivated H5N1 clade 2.3.2.1 reverse genetic (rgGD/2.3.2.1) vaccine given at 16 days of age, either as a single vaccination or in a prime-boost regime. At 30 days of age, ducks were challenged with one of two H5N1 HPAI viruses: A/duck/Vietnam/NCVD-2721/2013 (clade 1.1.2) or A/duck/Vietnam/NCVD-1584/2012 (clade 2.3.2.1.C). These viruses produced 100% mortality in less than 5 days in nonvaccinated control ducks. Ducks vaccinated with the rgGD/2.3.2.1 vaccine, with or without the rHVT-H5/2.2 vaccine, were 90%-100% protected against mortality after challenge with either of the two H5N1 HPAI viruses. The rHVT-H5/2.2 vaccine alone, however, conferred only 30% protection against mortality after challenge with either H5N1 HPAI virus; the surviving ducks from these groups shed higher amount of virus and for longer than the single-vaccinated rgGD/2.3.2.1 group. Despite low protection, ducks vaccinated with the rHVT-H5/2.2 vaccine and challenged with the clade 1.1.2 Vietnam virus had a longer mean death time than nonvaccinated controls (P = 0.02). A booster effect was found on reduction of virus shedding when using both vaccines, with lower oropharyngeal viral titers at 4 days after challenge with either HPAI virus (P study demonstrates the suboptimal protection with the rHVT-H5/2.2 vaccine given alone in Pekin ducks against H5N1 HPAI viruses and only a minor additive effect on virus shedding reduction when used with an inactivated vaccine in a

Prior infection of chickens with H1N1 or H1N2 avian influenza elicits partial heterologous protection against highly pathogenic H5N1.

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Nfon, Charles; Berhane, Yohannes; Pasick, John; Embury-Hyatt, Carissa; Kobinger, Gary; Kobasa, Darwyn; Babiuk, Shawn

2012-01-01

There is a critical need to have vaccines that can protect against emerging pandemic influenza viruses. Commonly used influenza vaccines are killed whole virus that protect against homologous and not heterologous virus. Using chickens we have explored the possibility of using live low pathogenic avian influenza (LPAI) A/goose/AB/223/2005 H1N1 or A/WBS/MB/325/2006 H1N2 to induce immunity against heterologous highly pathogenic avian influenza (HPAI) A/chicken/Vietnam/14/2005 H5N1. H1N1 and H1N2 replicated in chickens but did not cause clinical disease. Following infection, chickens developed nucleoprotein and H1 specific antibodies, and reduced H5N1 plaque size in vitro in the absence of H5 neutralizing antibodies at 21 days post infection (DPI). In addition, heterologous cell mediated immunity (CMI) was demonstrated by antigen-specific proliferation and IFN-γ secretion in PBMCs re-stimulated with H5N1 antigen. Following H5N1 challenge of both pre-infected and naïve controls chickens housed together, all naïve chickens developed acute disease and died while H1N1 or H1N2 pre-infected chickens had reduced clinical disease and 70-80% survived. H1N1 or H1N2 pre-infected chickens were also challenged with H5N1 and naïve chickens placed in the same room one day later. All pre-infected birds were protected from H5N1 challenge but shed infectious virus to naïve contact chickens. However, disease onset, severity and mortality was reduced and delayed in the naïve contacts compared to directly inoculated naïve controls. These results indicate that prior infection with LPAI virus can generate heterologous protection against HPAI H5N1 in the absence of specific H5 antibody.

Prior infection of chickens with H1N1 or H1N2 avian influenza elicits partial heterologous protection against highly pathogenic H5N1.

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Charles Nfon

Full Text Available There is a critical need to have vaccines that can protect against emerging pandemic influenza viruses. Commonly used influenza vaccines are killed whole virus that protect against homologous and not heterologous virus. Using chickens we have explored the possibility of using live low pathogenic avian influenza (LPAI A/goose/AB/223/2005 H1N1 or A/WBS/MB/325/2006 H1N2 to induce immunity against heterologous highly pathogenic avian influenza (HPAI A/chicken/Vietnam/14/2005 H5N1. H1N1 and H1N2 replicated in chickens but did not cause clinical disease. Following infection, chickens developed nucleoprotein and H1 specific antibodies, and reduced H5N1 plaque size in vitro in the absence of H5 neutralizing antibodies at 21 days post infection (DPI. In addition, heterologous cell mediated immunity (CMI was demonstrated by antigen-specific proliferation and IFN-γ secretion in PBMCs re-stimulated with H5N1 antigen. Following H5N1 challenge of both pre-infected and naïve controls chickens housed together, all naïve chickens developed acute disease and died while H1N1 or H1N2 pre-infected chickens had reduced clinical disease and 70-80% survived. H1N1 or H1N2 pre-infected chickens were also challenged with H5N1 and naïve chickens placed in the same room one day later. All pre-infected birds were protected from H5N1 challenge but shed infectious virus to naïve contact chickens. However, disease onset, severity and mortality was reduced and delayed in the naïve contacts compared to directly inoculated naïve controls. These results indicate that prior infection with LPAI virus can generate heterologous protection against HPAI H5N1 in the absence of specific H5 antibody.

Immune escape mutants of Highly Pathogenic Avian Influenza H5N1 selected using polyclonal sera: identification of key amino acids in the HA protein.

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Ioannis Sitaras

Full Text Available Evolution of Avian Influenza (AI viruses--especially of the Highly Pathogenic Avian Influenza (HPAI H5N1 subtype--is a major issue for the poultry industry. HPAI H5N1 epidemics are associated with huge economic losses and are sometimes connected to human morbidity and mortality. Vaccination (either as a preventive measure or as a means to control outbreaks is an approach that splits the scientific community, due to the risk of it being a potential driving force in HPAI evolution through the selection of mutants able to escape vaccination-induced immunity. It is therefore essential to study how mutations are selected due to immune pressure. To this effect, we performed an in vitro selection of mutants from HPAI A/turkey/Turkey/1/05 (H5N1, using immune pressure from homologous polyclonal sera. After 42 rounds of selection, we identified 5 amino acid substitutions in the Haemagglutinin (HA protein, most of which were located in areas of antigenic importance and suspected to be prone to selection pressure. We report that most of the mutations took place early in the selection process. Finally, our antigenic cartography studies showed that the antigenic distance between the selected isolates and their parent strain increased with passage number.

Efficacy of two H5N9-inactivated vaccines against challenge with a recent H5N1 highly pathogenic avian influenza isolate from a chicken in Thailand.

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Bublot, Michel; Le Gros, François-Xavier; Nieddu, Daniela; Pritchard, Nikki; Mickle, Thomas R; Swayne, David E

2007-03-01

The objective of this study was to compare the efficacy of two avian influenza (AI) H5-inactivated vaccines containing either an American (A/turkey/Wisconsin/68 H5N9; H5N9-WI) or a Eurasian isolate (A/chicken/Italy/22A/98 H5N9; H5N9-It). Three-week-old specific pathogen-free chickens were vaccinated once and challenged 3 wk later with a H5N1 highly pathogenic AI (HPAI) virus isolated from a chicken in Thailand in 2004. All unvaccinated challenged birds died within 2 days, whereas 90% and 100% of chickens vaccinated with H5N9-WI and H5N9-It, respectively, were protected against morbidity and mortality. Both vaccines prevented cloacal shedding and significantly reduced oral shedding of the challenge HPAI virus. Additional chickens (vaccinated or unvaccinated) were placed in contact with the directly challenged birds 18 hr after challenge. All unvaccinated chickens in contact with unvaccinated challenged birds died within 3 days after contact, whereas unvaccinated chickens in contact with vaccinated challenged birds either showed a significantly delayed mortality or did not become infected. All vaccinated contacts were protected against clinical signs, and most chickens did not shed detectable amount of HPAI virus. Altogether, these data indicate that both vaccines protected very well against morbidity and mortality and reduced or prevented shedding induced by direct or contact exposure to Asian H5N1 HPAI virus.

Using knowledge fusion to analyze avian influenza H5N1 in East and Southeast Asia.

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Erjia Ge

Full Text Available Highly pathogenic avian influenza (HPAI H5N1, a disease associated with high rates of mortality in infected human populations, poses a serious threat to public health in many parts of the world. This article reports findings from a study aimed at improving our understanding of the spatial pattern of the highly pathogenic avian influenza, H5N1, risk in East-Southeast Asia where the disease is both persistent and devastating. Though many disciplines have made important contributions to our understanding of H5N1, it remains a challenge to integrate knowledge from different disciplines. This study applies genetic analysis that identifies the evolution of the H5N1 virus in space and time, epidemiological analysis that determines socio-ecological factors associated with H5N1 occurrence, and statistical analysis that identifies outbreak clusters, and then applies a methodology to formally integrate the findings of the three sets of methodologies. The present study is novel in two respects. First it makes the initiative attempt to use genetic sequences and space-time data to create a space-time phylogenetic tree to estimate and map the virus' ability to spread. Second, by integrating the results we are able to generate insights into the space-time occurrence and spread of H5N1 that we believe have a higher level of corroboration than is possible when analysis is based on only one methodology. Our research identifies links between the occurrence of H5N1 by area and a set of socio-ecological factors including altitude, population density, poultry density, and the shortest path distances to inland water, coastlines, migrating routes, railways, and roads. This study seeks to lay a solid foundation for the interdisciplinary study of this and other influenza outbreaks. It will provide substantive information for containing H5N1 outbreaks.

Using knowledge fusion to analyze avian influenza H5N1 in East and Southeast Asia.

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Ge, Erjia; Haining, Robert; Li, Chi Pang; Yu, Zuguo; Waye, Miu Yee; Chu, Ka Hou; Leung, Yee

2012-01-01

Highly pathogenic avian influenza (HPAI) H5N1, a disease associated with high rates of mortality in infected human populations, poses a serious threat to public health in many parts of the world. This article reports findings from a study aimed at improving our understanding of the spatial pattern of the highly pathogenic avian influenza, H5N1, risk in East-Southeast Asia where the disease is both persistent and devastating. Though many disciplines have made important contributions to our understanding of H5N1, it remains a challenge to integrate knowledge from different disciplines. This study applies genetic analysis that identifies the evolution of the H5N1 virus in space and time, epidemiological analysis that determines socio-ecological factors associated with H5N1 occurrence, and statistical analysis that identifies outbreak clusters, and then applies a methodology to formally integrate the findings of the three sets of methodologies. The present study is novel in two respects. First it makes the initiative attempt to use genetic sequences and space-time data to create a space-time phylogenetic tree to estimate and map the virus' ability to spread. Second, by integrating the results we are able to generate insights into the space-time occurrence and spread of H5N1 that we believe have a higher level of corroboration than is possible when analysis is based on only one methodology. Our research identifies links between the occurrence of H5N1 by area and a set of socio-ecological factors including altitude, population density, poultry density, and the shortest path distances to inland water, coastlines, migrating routes, railways, and roads. This study seeks to lay a solid foundation for the interdisciplinary study of this and other influenza outbreaks. It will provide substantive information for containing H5N1 outbreaks.

Pathogenicity of the Korean H5N8 highly pathogenic avian influenza virus in commercial domestic poultry species.

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Lee, Dong-Hun; Kwon, Jung-Hoon; Noh, Jin-Yong; Park, Jae-Keun; Yuk, Seong-Su; Erdene-Ochir, Tseren-Ochir; Lee, Joong-Bok; Park, Seung-Yong; Choi, In-Soo; Lee, Sang-Won; Song, Chang-Seon

2016-01-01

In 2014, the highly pathogenic avian influenza (HPAI) virus H5N8 triggered outbreaks in wild birds and poultry farms in South Korea. In the present study, we investigated the pathogenicity of the H5N8 HPAI virus, belonging to the clade 2.3.4.4, in different species of poultry. For this, we examined clinical signs and viral shedding levels following intranasal inoculation of the virus in 3-week-old commercial layer chickens and quails, 10-week-old Korean native chickens, and 8-week-old Muscovy ducks. Intranasal inoculation with 10(6.0) viruses at 50% egg-infective dose resulted in 100% mortality in the layer chickens (8/8) and quails (4/4), but 60% and 0% deaths in the Korean native chickens (3/5) and Muscovy ducks (0/4), respectively. In addition, transmission of the inoculated virus to contact-exposed birds was evident in all the species used in this study. Based on our results, we conclude that the H5N8 HPAI virus has lower pathogenicity and transmissibility in poultry species compared with previously reported H5N1 HPAI viruses.

Protection of White Leghorn chickens by U.S. emergency H5 vaccination against clade 2.3.4.4 H5N2 high pathogenicity avian influenza virus.

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Bertran, Kateri; Balzli, Charles; Lee, Dong-Hun; Suarez, David L; Kapczynski, Darrell R; Swayne, David E

2017-11-01

During December 2014-June 2015, the U.S. experienced a high pathogenicity avian influenza (HPAI) outbreak caused by clade 2.3.4.4 H5Nx Goose/Guangdong lineage viruses with devastating consequences for the poultry industry. Three vaccines, developed based on updating existing registered vaccines or currently licensed technologies, were evaluated for possible use: an inactivated reverse genetics H5N1 vaccine (rgH5N1) and an RNA particle vaccine (RP-H5), both containing the hemagglutinin gene of clade 2.3.4.4 strain, and a recombinant herpesvirus turkey vectored vaccine (rHVT-H5) containing the hemagglutinin gene of clade 2.2 strain. The efficacy of the three vaccines, alone or in combination, was assessed in White Leghorn chickens against clade 2.3.4.4 H5N2 HPAI virus challenge. In Study 1, single (rHVT-H5) and prime-boost (rHVT-H5+rgH5N1 or rHVT-H5+RP-H5) vaccination strategies protected chickens with high levels of protective immunity and significantly reduced virus shedding. In Study 2, single vaccination with either rgH5N1 or RP-H5 vaccines provided clinical protection in adult chickens and significantly reduced virus shedding. In Study 3, double rgH5N1 vaccination protected adult chickens from clinical signs and mortality when challenged 20weeks post-boost, with high levels of long-lasting protective immunity and significantly reduced virus shedding. These studies support the use of genetically related vaccines, possibly in combination with a broad protective priming vaccine, for emergency vaccination programs against clade 2.3.4.4 H5Nx HPAI virus in young and adult layer chickens. Published by Elsevier Ltd.

Characterizing wild bird contact and seropositivity to highly pathogenic avian influenza A (H5N1) virus in Alaskan residents.

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Reed, Carrie; Bruden, Dana; Byrd, Kathy K; Veguilla, Vic; Bruce, Michael; Hurlburt, Debby; Wang, David; Holiday, Crystal; Hancock, Kathy; Ortiz, Justin R; Klejka, Joe; Katz, Jacqueline M; Uyeki, Timothy M

2014-09-01

Highly pathogenic avian influenza A (HPAI) H5N1 viruses have infected poultry and wild birds on three continents with more than 600 reported human cases (59% mortality) since 2003. Wild aquatic birds are the natural reservoir for avian influenza A viruses, and migratory birds have been documented with HPAI H5N1 virus infection. Since 2005, clade 2.2 HPAI H5N1 viruses have spread from Asia to many countries. We conducted a cross-sectional seroepidemiological survey in Anchorage and western Alaska to identify possible behaviors associated with migratory bird exposure and measure seropositivity to HPAI H5N1. We enrolled rural subsistence bird hunters and their families, urban sport hunters, wildlife biologists, and a comparison group without bird contact. We interviewed participants regarding their exposures to wild birds and collected blood to perform serologic testing for antibodies against a clade 2.2 HPAI H5N1 virus strain. Hunters and wildlife biologists reported exposures to wild migratory birds that may confer risk of infection with avian influenza A viruses, although none of the 916 participants had evidence of seropositivity to HPAI H5N1. We characterized wild bird contact among Alaskans and behaviors that may influence risk of infection with avian influenza A viruses. Such knowledge can inform surveillance and risk communication surrounding HPAI H5N1 and other influenza viruses in a population with exposure to wild birds at a crossroads of intercontinental migratory flyways. © 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Avian influenza virus (H5N1; effects of physico-chemical factors on its survival

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Hameed Sajid

2009-03-01

Full Text Available Abstract Present study was performed to determine the effects of physical and chemical agents on infective potential of highly pathogenic avian influenza (HPAI H5N1 (local strain virus recently isolated in Pakistan during 2006 outbreak. H5N1 virus having titer 108.3 ELD50/ml was mixed with sterilized peptone water to get final dilution of 4HA units and then exposed to physical (temperature, pH and ultraviolet light and chemical (formalin, phenol crystals, iodine crystals, CID 20, virkon®-S, zeptin 10%, KEPCIDE 300, KEPCIDE 400, lifebuoy, surf excel and caustic soda agents. Harvested amnio-allantoic fluid (AAF from embryonated chicken eggs inoculated with H5N1 treated virus (0.2 ml/egg was subjected to haemagglutination (HA and haemagglutination inhibition (HI tests. H5N1 virus lost infectivity after 30 min at 56°C, after 1 day at 28°C but remained viable for more than 100 days at 4°C. Acidic pH (1, 3 and basic pH (11, 13 were virucidal after 6 h contact time; however virus retained infectivity at pH 5 (18 h, 7 and 9 (more than 24 h. UV light was proved ineffectual in inactivating virus completely even after 60 min. Soap (lifebuoy®, detergent (surf excel® and alkali (caustic soda destroyed infectivity after 5 min at 0.1, 0.2 and 0.3% dilution. All commercially available disinfectants inactivated virus at recommended concentrations. Results of present study would be helpful in implementing bio-security measures at farms/hatcheries levels in the wake of avian influenza virus (AIV outbreak.

75 FR 69046 - Notice of Determination of the High Pathogenic Avian Influenza Subtype H5N1 Status of Czech...

Science.gov (United States)

2010-11-10

... Avian Influenza Subtype H5N1 Status of Czech Republic and Sweden AGENCY: Animal and Plant Health... the highly pathogenic avian influenza (HPAI) subtype H5N1 status of the Czech Republic and Sweden... status of the Czech Republic and Sweden relative to highly pathogenic avian influenza (HPAI) subtype H5N1...

Southward autumn migration of waterfowl facilitates cross-continental transmission of the highly pathogenic avian influenza H5N1 virus

NARCIS (Netherlands)

Xu, Yanjie; Gong, Peng; Wielstra, Ben; Si, Yali

2016-01-01

The highly pathogenic avian influenza subtype H5N1 (HPAI H5N1) is a worldwide zoonotic infectious disease, threatening humans, poultry and wild birds. The role of wild birds in the spread of HPAI H5N1 has previously been investigated by comparing disease spread patterns with bird migration

Migration of whooper swans and outbreaks of highly pathogenic avian influenza H5N1 virus in eastern Asia.

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Newman, Scott H; Iverson, Samuel A; Takekawa, John Y; Gilbert, Martin; Prosser, Diann J; Batbayar, Nyambyar; Natsagdorj, Tseveenmyadag; Douglas, David C

2009-05-28

Evaluating the potential involvement of wild avifauna in the emergence of highly pathogenic avian influenza H5N1 (hereafter H5N1) requires detailed analyses of temporal and spatial relationships between wild bird movements and disease emergence. The death of wild swans (Cygnus spp.) has been the first indicator of the presence of H5N1 in various Asian and European countries; however their role in the geographic spread of the disease remains poorly understood. We marked 10 whooper swans (Cygnus cygnus) with GPS transmitters in northeastern Mongolia during autumn 2006 and tracked their migratory movements in relation to H5N1 outbreaks. The prevalence of H5N1 outbreaks among poultry in eastern Asia during 2003-2007 peaked during winter, concurrent with whooper swan movements into regions of high poultry density. However outbreaks involving poultry were detected year round, indicating disease perpetuation independent of migratory waterbird presence. In contrast, H5N1 outbreaks involving whooper swans, as well as other migratory waterbirds that succumbed to the disease in eastern Asia, tended to occur during seasons (late spring and summer) and in habitats (areas of natural vegetation) where their potential for contact with poultry is very low to nonexistent. Given what is known about the susceptibility of swans to H5N1, and on the basis of the chronology and rates of whooper swan migration movements, we conclude that although there is broad spatial overlap between whooper swan distributions and H5N1 outbreak locations in eastern Asia, the likelihood of direct transmission between these groups is extremely low. Thus, our data support the hypothesis that swans are best viewed as sentinel species, and moreover, that in eastern Asia, it is most likely that their infections occurred through contact with asymptomatic migratory hosts (e.g., wild ducks) at or near their breeding grounds.

Infectivity, transmission and pathogenicity of H5 highly pathogenic avian influenza clade 2.3.4.4 (H5N8 and H5N2) United States index viruses in Pekin ducks and Chinese geese

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In late 2014, a H5N8 highly pathogenic avian influenza (HPAI) virus, clade 2.3.4.4, spread by migratory birds into North America mixing with low pathogenicity AI viruses to produce a H5N2 HPAI virus. The H5N8 and H5N2 HPAI viruses were detected initially in wild waterfowl and backyard birds, and lat...

Unique Infectious Strategy of H5N1 Avian Influenza Virus Is Governed by the Acid-Destabilized Property of Hemagglutinin.

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Daidoji, Tomo; Watanabe, Yohei; Arai, Yasuha; Kajikawa, Junichi; Hirose, Ryohei; Nakaya, Takaaki

Highly pathogenic avian influenza (HPAI) H5N1 virus emerged in 1997 as a zoonotic disease in Hong Kong. It has since spread to Asia and Europe and is a serious threat to both the poultry industry and human health. For effective surveillance and possible prevention/control of HPAI H5N1 viruses, it is necessary to understand the molecular mechanism underlying HPAI H5N1 pathogenesis. The hemagglutinin (HA) protein of influenza A viruses (IAVs) is one of the major determinants of host adaptation, transmissibility, and viral virulence. The main function of the HA protein is to facilitate viral entry and viral genome release within host cells before infection. To achieve viral infection, IAVs belonging to different subtypes or strains induce viral-cell membrane fusion at different endosomal pH levels after internalization through endocytosis. However, host-specific endosomal pH also affects induction of membrane fusion followed by infection. The HA protein of HPAI H5N1 has a higher pH threshold for membrane fusion than the HA protein of classical avian influenza viruses. Although this particular property of HA (which governs viral infection) is prone to deactivation in the avian intestine or in an ambient environment, it facilitates efficient infection of host cells, resulting in a broad host tropism, regardless of the pH in the host endosome. Accumulated knowledge, together with further research, about the HA-governed mechanism underlying HPAI H5N1 virulence (i.e., receptor tropism and pH-dependent viral-cell membrane fusion) will be helpful for developing effective surveillance strategies and for prevention/control of HPAI H5N1 infection.

Experimental infection of swans and geese with highly pathogenic avian influenza virus (H5N1) of Asian lineage.

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Brown, Justin D; Stallknecht, David E; Swayne, David E

2008-01-01

The role of wild birds in the epidemiology of the Asian lineage highly pathogenic avian influenza (HPAI) virus subtype H5N1 epizootic and their contribution to the spread of the responsible viruses in Eurasia and Africa are unclear. To better understand the potential role of swans and geese in the epidemiology of this virus, we infected 4 species of swans and 2 species of geese with an HPAI virus of Asian lineage recovered from a whooper swan in Mongolia in 2005, A/whooper swan/Mongolia/244/2005 (H5N1). The highest mortality rates were observed in swans, and species-related differences in clinical illness and viral shedding were evident. These results suggest that the potential for HPAI (H5N1) viral shedding and the movement of infected birds may be species-dependent and can help explain observed deaths associated with HPAI (H5N1) infection in anseriforms in Eurasia.

Influenza A H5N1 clade 2.3.4 virus with a different antiviral susceptibility profile replaced clade 1 virus in humans in northern Vietnam.

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Mai T Q Le

2008-10-01

Full Text Available Prior to 2007, highly pathogenic avian influenza (HPAI H5N1 viruses isolated from poultry and humans in Vietnam were consistently reported to be clade 1 viruses, susceptible to oseltamivir but resistant to amantadine. Here we describe the re-emergence of human HPAI H5N1 virus infections in Vietnam in 2007 and the characteristics of the isolated viruses.Respiratory specimens from patients suspected to be infected with avian influenza in 2007 were screened by influenza and H5 subtype specific polymerase chain reaction. Isolated H5N1 strains were further characterized by genome sequencing and drug susceptibility testing. Eleven poultry outbreak isolates from 2007 were included in the sequence analysis. Eight patients, all of them from northern Vietnam, were diagnosed with H5N1 in 2007 and five of them died. Phylogenetic analysis of H5N1 viruses isolated from humans and poultry in 2007 showed that clade 2.3.4 H5N1 viruses replaced clade 1 viruses in northern Vietnam. Four human H5N1 strains had eight-fold reduced in-vitro susceptibility to oseltamivir as compared to clade 1 viruses. In two poultry isolates the I117V mutation was found in the neuraminidase gene, which is associated with reduced susceptibility to oseltamivir. No mutations in the M2 gene conferring amantadine resistance were found.In 2007, H5N1 clade 2.3.4 viruses replaced clade 1 viruses in northern Vietnam and were susceptible to amantadine but showed reduced susceptibility to oseltamivir. Combination antiviral therapy with oseltamivir and amantadine for human cases in Vietnam is recommended.

Corneal Opacity in Domestic Ducks Experimentally Infected With H5N1 Highly Pathogenic Avian Influenza Virus.

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Yamamoto, Y; Nakamura, K; Yamada, M; Mase, M

2016-01-01

Domestic ducks can be a key factor in the regional spread of H5N1 highly pathogenic avian influenza (HPAI) virus in Asia. The authors performed experimental infections to examine the relationship between corneal opacity and H5N1 HPAI virus infection in domestic ducks (Anas platyrhyncha var domestica). A total of 99 domestic ducks, including 3 control birds, were used in the study. In experiment 1, when domestic ducks were inoculated intranasally with 2 H5N1 HPAI viruses, corneal opacity appeared more frequently than neurologic signs and mortality. Corneal ulceration and exophthalmos were rare findings. Histopathologic examinations of the eyes of domestic ducks in experiment 2 revealed that corneal opacity was due to the loss of corneal endothelial cells and subsequent keratitis with edema. Influenza viral antigen was detected in corneal endothelial cells and some other ocular cells by immunohistochemistry. Results suggest that corneal opacity is a characteristic and frequent finding in domestic ducks infected with the H5N1 HPAI virus. Confirming this ocular change may improve the detection rate of infected domestic ducks in the field. © The Author(s) 2015.

Southward autumn migration of waterfowl facilitates cross-continental transmission of the highly pathogenic avian influenza H5N1 virus

Science.gov (United States)

Xu, Yanjie; Gong, Peng; Wielstra, Ben; Si, Yali

2016-08-01

The highly pathogenic avian influenza subtype H5N1 (HPAI H5N1) is a worldwide zoonotic infectious disease, threatening humans, poultry and wild birds. The role of wild birds in the spread of HPAI H5N1 has previously been investigated by comparing disease spread patterns with bird migration routes. However, the different roles that the southward autumn and northward spring migration might play in virus transmission have hardly been explored. Using direction analysis, we analyze HPAI H5N1 transmission directions and angular concentration of currently circulating viral clades, and compare these with waterfowl seasonal migration directions along major waterfowl flyways. Out of 22 HPAI H5N1 transmission directions, 18 had both a southward direction and a relatively high concentration. Differences between disease transmission and waterfowl migration directions were significantly smaller for autumn than for spring migration. The four northward transmission directions were found along Asian flyways, where the initial epicenter of the virus was located. We suggest waterfowl first picked up the virus from East Asia, then brought it to the north via spring migration, and then spread it to other parts of world mainly by autumn migration. We emphasize waterfowl autumn migration plays a relatively important role in HPAI H5N1 transmission compared to spring migration.

Characterization of Clade 2.3.2.1 H5N1 Highly Pathogenic Avian Influenza Viruses Isolated from Wild Birds (Mandarin Duck and Eurasian Eagle Owl in 2010 in Korea

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Youn-Jeong Lee

2013-04-01

Full Text Available Starting in late November 2010, the H5N1 highly pathogenic avian influenza (HPAI virus was isolated from many types of wild ducks and raptors and was subsequently isolated from poultry in Korea. We assessed the genetic and pathogenic properties of the HPAI viruses isolated from a fecal sample from a mandarin duck and a dead Eurasian eagle owl, the most affected wild bird species during the 2010/2011 HPAI outbreak in Korea. These viruses have similar genetic backgrounds and exhibited the highest genetic similarity with recent Eurasian clade 2.3.2.1 HPAI viruses. In animal inoculation experiments, regardless of their originating hosts, the two Korean isolates produced highly pathogenic characteristics in chickens, ducks and mice without pre-adaptation. These results raise concerns about veterinary and public health. Surveillance of wild birds could provide a good early warning signal for possible HPAI infection in poultry as well as in humans.

Migration of whooper swans and outbreaks of highly pathogenic avian influenza H5N1 virus in eastern Asia.

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Scott H Newman

Full Text Available Evaluating the potential involvement of wild avifauna in the emergence of highly pathogenic avian influenza H5N1 (hereafter H5N1 requires detailed analyses of temporal and spatial relationships between wild bird movements and disease emergence. The death of wild swans (Cygnus spp. has been the first indicator of the presence of H5N1 in various Asian and European countries; however their role in the geographic spread of the disease remains poorly understood. We marked 10 whooper swans (Cygnus cygnus with GPS transmitters in northeastern Mongolia during autumn 2006 and tracked their migratory movements in relation to H5N1 outbreaks. The prevalence of H5N1 outbreaks among poultry in eastern Asia during 2003-2007 peaked during winter, concurrent with whooper swan movements into regions of high poultry density. However outbreaks involving poultry were detected year round, indicating disease perpetuation independent of migratory waterbird presence. In contrast, H5N1 outbreaks involving whooper swans, as well as other migratory waterbirds that succumbed to the disease in eastern Asia, tended to occur during seasons (late spring and summer and in habitats (areas of natural vegetation where their potential for contact with poultry is very low to nonexistent. Given what is known about the susceptibility of swans to H5N1, and on the basis of the chronology and rates of whooper swan migration movements, we conclude that although there is broad spatial overlap between whooper swan distributions and H5N1 outbreak locations in eastern Asia, the likelihood of direct transmission between these groups is extremely low. Thus, our data support the hypothesis that swans are best viewed as sentinel species, and moreover, that in eastern Asia, it is most likely that their infections occurred through contact with asymptomatic migratory hosts (e.g., wild ducks at or near their breeding grounds.

A highly pathogenic avian influenza virus H5N1 with 2009 pandemic H1N1 internal genes demonstrated increased replication and transmission in pigs

Science.gov (United States)

This study investigated the pathogenicity and transmissibility of a reverse-genetics derived highly pathogenic avian influenza (HPAI) H5N1 influenza A virus (IAV), A/Iraq/775/06, and a reassortant virus comprised of the HA and NA from A/Iraq/775/06 and the internal genes of a 2009 pandemic H1N1, A/N...

Comparison of ARIMA and Random Forest time series models for prediction of avian influenza H5N1 outbreaks.

Science.gov (United States)

Kane, Michael J; Price, Natalie; Scotch, Matthew; Rabinowitz, Peter

2014-08-13

Time series models can play an important role in disease prediction. Incidence data can be used to predict the future occurrence of disease events. Developments in modeling approaches provide an opportunity to compare different time series models for predictive power. We applied ARIMA and Random Forest time series models to incidence data of outbreaks of highly pathogenic avian influenza (H5N1) in Egypt, available through the online EMPRES-I system. We found that the Random Forest model outperformed the ARIMA model in predictive ability. Furthermore, we found that the Random Forest model is effective for predicting outbreaks of H5N1 in Egypt. Random Forest time series modeling provides enhanced predictive ability over existing time series models for the prediction of infectious disease outbreaks. This result, along with those showing the concordance between bird and human outbreaks (Rabinowitz et al. 2012), provides a new approach to predicting these dangerous outbreaks in bird populations based on existing, freely available data. Our analysis uncovers the time-series structure of outbreak severity for highly pathogenic avain influenza (H5N1) in Egypt.

Demographic and clinical predictors of mortality from highly pathogenic avian influenza A (H5N1 virus infection: CART analysis of international cases.

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Rita B Patel

Full Text Available Human infections with highly pathogenic avian influenza (HPAI A (H5N1 viruses have occurred in 15 countries, with high mortality to date. Determining risk factors for morbidity and mortality from HPAI H5N1 can inform preventive and therapeutic interventions.We included all cases of human HPAI H5N1 reported in World Health Organization Global Alert and Response updates and those identified through a systematic search of multiple databases (PubMed, Scopus, and Google Scholar, including articles in all languages. We abstracted predefined clinical and demographic predictors and mortality and used bivariate logistic regression analyses to examine the relationship of each candidate predictor with mortality. We developed and pruned a decision tree using nonparametric Classification and Regression Tree methods to create risk strata for mortality.We identified 617 human cases of HPAI H5N1 occurring between December 1997 and April 2013. The median age of subjects was 18 years (interquartile range 6-29 years and 54% were female. HPAI H5N1 case-fatality proportion was 59%. The final decision tree for mortality included age, country, per capita government health expenditure, and delay from symptom onset to hospitalization, with an area under the receiver operator characteristic (ROC curve of 0.81 (95% CI: 0.76-0.86.A model defined by four clinical and demographic predictors successfully estimated the probability of mortality from HPAI H5N1 illness. These parameters highlight the importance of early diagnosis and treatment and may enable early, targeted pharmaceutical therapy and supportive care for symptomatic patients with HPAI H5N1 virus infection.

No evidence of transmission of H5N1 highly pathogenic avian influenza to humans after unprotected contact with infected wild swans.

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Wallensten, A; Salter, M; Bennett, S; Brown, I; Hoschler, K; Oliver, I

2010-02-01

Highly pathogenic avian influenza (HPAI) subtype H5N1 remains a public health threat as long as it circulates in wild and domestic birds. Information on the transmissibility of H5N1 HPAI from wild birds is needed for evidence-based public health advice. We investigated if transmission of H5N1 HPAI had taken place in people that had unprotected contact with infected wild mute swans during an incident at the Abbotsbury Swannery in Dorset, England. Thirteen people who had been exposed to infected swans were contacted and actively followed up for symptoms. Serology was taken after 30 days. We did not find evidence of transmission of H5N1 HPAI to humans during the incident. The incident provided a rare opportunity to study the transmissibility of the virus from wild birds to humans.

Variable epidemiology of the three outbreaks of unrelated highly pathogenic avian influenza viruses in the United States, 2014-2017

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Three unrelated highly pathogenic avian influenza (HPAI) outbreaks have occurred in the United States (US) during 2014-2017. Late in 2014, Canada reported the first outbreak of an H5N2 reassortment virus between the A/goose/Guangdong/1/1996 (Gs/GD)-lineage H5Nx clade 2.3.4.4A HPAI and North American...

Isolation and genetic characterization of a novel 2.2.1.2a H5N1 virus from a vaccinated meat-turkeys flock in Egypt.

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Salaheldin, Ahmed H; Veits, Jutta; Abd El-Hamid, Hatem S; Harder, Timm C; Devrishov, Davud; Mettenleiter, Thomas C; Hafez, Hafez M; Abdelwhab, Elsayed M

2017-03-09

Vaccination of poultry to control highly pathogenic avian influenza virus (HPAIV) H5N1 is used in several countries. HPAIV H5N1 of clade 2.2.1 which is endemic in Egypt has diversified into two genetic clades. Clade 2.2.1.1 represents antigenic drift variants in vaccinated commercial poultry while clade 2.2.1.2 variants are detected in humans and backyard poultry. Little is known about H5N1 infection in vaccinated turkeys under field conditions. Here, we describe an HPAI H5N1 outbreak in a vaccinated meat-turkey flock in Egypt. Birds were vaccinated with inactivated H5N2 and H5N1 vaccines at 8 and 34 days of age, respectively. At 72 nd day of age (38 days post last vaccination), turkeys exhibited mild respiratory signs, cyanosis of snood and severe congestion of the internal organs. Survivors had a reduction in feed consumption and body gain. A mortality of ~29% cumulated within 10 days after the onset of clinical signs. Laboratory diagnosis using RT-qPCRs revealed presence of H5N1 but was negative for H7 and H9 subtypes. A substantial antigenic drift against different serum samples from clade 2.2.1.1 and clade 2.3.4.4 was observed. Based on full genome sequence analysis the virus belonged to clade 2.2.1.2 but clustered with recent H5N1 viruses from 2015 in poultry in Israel, Gaza and Egypt in a novel subclade designated here 2.2.1.2a which is distinct from 2014/2015 2.2.1.2 viruses. These viruses possess 2.2.1.2 clade-specific genetic signatures and also mutations in the HA similar to those in clade 2.2.1.1 that enabled evasion from humoral immune response. Taken together, this manuscript describes a recent HPAI H5N1 outbreak in vaccinated meat-turkeys in Egypt after infection with a virus representing novel distinct 2.2.1.2a subclade. Infection with HPAIV H5N1 in commercial turkeys resulted in significant morbidity and mortality despite of vaccination using H5 vaccines. The isolated virus showed antigenic drift and clustered in a novel cluster designated here

Highly Pathogenic Avian Influenza H5N8 Clade 2.3.4.4b in Germany in 2016/2017

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Anja Globig

2018-01-01

Full Text Available Here, we report on the occurrence of highly pathogenic avian influenza (HPAI H5Nx clade 2.3.4.4b in Germany. Between November 8, 2016, and September 30, 2017, more than 1,150 cases of HPAI H5Nx clade 2.3.4.4b in wild birds and 107 outbreaks in birds kept in captivity (92 poultry holdings and 15 zoos/animal parks were reported in Germany. This HPAI epidemic is the most severe recorded in Germany so far. The viruses were apparently introduced by migratory birds, sparking an epidemic among wild birds across Germany with occasional incursions into poultry holdings, zoos and animal parks, which were usually rapidly detected and controlled by stamping out. HPAI viruses (mainly subtype H5N8, in a few cases also H5N5 were found in dead wild birds of at least 53 species. The affected wild birds were water birds (including gulls, storks, herons, and cormorants and scavenging birds (birds of prey, owls, and crows. In a number of cases, substantial gaps in farm biosecurity may have eased virus entry into the holdings. In a second wave of the epidemic starting from February 2017, there was epidemiological and molecular evidence for virus transmission of the infections between commercial turkey holdings in an area of high poultry density, which caused approximately 25% of the total number of outbreaks in poultry. Biosecurity measures in poultry holdings should be adapted. This includes, inter alia, wearing of stable-specific protective clothing and footwear, cleaning, and disinfection of equipment that has been in contact with birds and prevention of contacts between poultry and wild water birds.

Highly pathogenic influenza A(H5N1 virus survival in complex artificial aquatic biotopes.

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Viseth Srey Horm

Full Text Available BACKGROUND: Very little is known regarding the persistence of Highly Pathogenic Avian Influenza (HPAI H5N1 viruses in aquatic environments in tropical countries, although environmental materials have been suggested to play a role as reservoirs and sources of transmission for H5N1 viruses. METHODOLOGY/PRINCIPAL FINDINGS: The survival of HPAI H5N1 viruses in experimental aquatic biotopes (water, mud, aquatic flora and fauna relevant to field conditions in Cambodia was investigated. Artificial aquatic biotopes, including simple ones containing only mud and water, and complex biotopes involving the presence of aquatic flora and fauna, were set up. They were experimentally contaminated with H5N1 virus. The persistence of HPAI H5N1 virus (local avian and human isolates was determined by virus isolation in embryonated chicken eggs and by real-time reverse-polymerase chain reaction. Persistence of infectious virus did not exceed 4 days, and was only identified in rain water. No infectious virus particles were detected in pond and lake water or mud even when high inoculum doses were used. However, viral RNA persisted up to 20 days in rain water and 7 days in pond or lake water. Viral RNA was also detected in mud samples, up to 14 days post-contamination in several cases. Infectious virus and viral RNA was detected in few cases in the aquatic fauna and flora, especially in bivalves and labyrinth fish, although these organisms seemed to be mostly passive carriers of the virus rather than host allowing virus replication. CONCLUSIONS/SIGNIFICANCE: Although several factors for the survival and persistence of HPAI viruses in the environment are still to be elucidated, and are particularly hard to control in laboratory conditions, our results, along with previous data, support the idea that environmental surveillance is of major relevance for avian influenza control programs.

Prototype of A/Duck/Sukoharjo/Bbvw-1428-9/2012 subtipe H5N1 clade 2.3.2 as vaccine on local duck

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Risa Indriani

2014-06-01

Full Text Available A/Duck/Sukoharjo/Bbvw-1428-9/2012 virus subtipe H5N1 clade 2.3.2 as seed vaccine on local duck. AI H5N1 clade 2.3.2 vaccine containing 256 HAU per dose was formulated using adjuvant ISA 71VG Montanide ™. Six groups of one day old local duck were used in this study. Three groups (10 ducks per group were vaccinated and 3 groups (9 duck per group were served control. Vaccination was conducted when the duck were three weeks old of age using single dose. Three weeks after vaccination when the duck were challenged either with HPAI H5N1 clade 2.3.2, or HPAI H5N1 clade 2.1.3 virus at dose 106 EID50/ 0.1 ml by drops intranasaly. Result showed that vaccination produced 100% protection compared to unvaccinated ducks againt HPAI subtipe H5N1 clade 2.3.2, and 100% protection againt HPAI H5N1 clade 2.1.3 (A/ck/wj/Subang-29/2007 and A/ck/wj/Smi-Part/2006, while unvaccinated ducks showed virus shedding on day 3 post infection.

Influenza A H5N1 clade 2.3.4 virus with a different antiviral susceptibility profile replaced clade 1 virus in humans in northern Vietnam

NARCIS (Netherlands)

Le, Mai T. Q.; Wertheim, Heiman F. L.; Nguyen, Hien D.; Taylor, Walter; Hoang, Phuong V. M.; Vuong, Cuong D.; Nguyen, Hang L. K.; Nguyen, Ha H.; Nguyen, Thai Q.; Nguyen, Trung V.; van, Trang D.; Ngoc, Bich T.; Bui, Thinh N.; Nguyen, Binh G.; Nguyen, Liem T.; Luong, San T.; Phan, Phuc H.; Pham, Hung V.; Nguyen, Tung; Fox, Annette; Nguyen, Cam V.; Do, Ha Q.; Crusat, Martin; Farrar, Jeremy; Nguyen, Hien T.; de Jong, Menno D.; Horby, Peter

2008-01-01

BACKGROUND: Prior to 2007, highly pathogenic avian influenza (HPAI) H5N1 viruses isolated from poultry and humans in Vietnam were consistently reported to be clade 1 viruses, susceptible to oseltamivir but resistant to amantadine. Here we describe the re-emergence of human HPAI H5N1 virus infections

Highly (H5N1 and low (H7N2 pathogenic avian influenza virus infection in falcons via nasochoanal route and ingestion of experimentally infected prey.

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Kateri Bertran

Full Text Available An experimental infection with highly pathogenic avian influenza (HPAI and low pathogenic avian influenza (LPAI viruses was carried out on falcons in order to examine the effects of these viruses in terms of pathogenesis, viral distribution in tissues and viral shedding. The distribution pattern of influenza virus receptors was also assessed. Captive-reared gyr-saker (Falco rusticolus x Falco cherrug hybrid falcons were challenged with a HPAI H5N1 virus (A/Great crested grebe/Basque Country/06.03249/2006 or a LPAI H7N2 virus (A/Anas plathyrhynchos/Spain/1877/2009, both via the nasochoanal route and by ingestion of previously infected specific pathogen free chicks. Infected falcons exhibited similar infection dynamics despite the different routes of exposure, demonstrating the effectiveness of in vivo feeding route. H5N1 infected falcons died, or were euthanized, between 5-7 days post-infection (dpi after showing acute severe neurological signs. Presence of viral antigen in several tissues was confirmed by immunohistochemistry and real time RT-PCR (RRT-PCR, which were generally associated with significant microscopical lesions, mostly in the brain. Neither clinical signs, nor histopathological findings were observed in any of the H7N2 LPAI infected falcons, although all of them had seroconverted by 11 dpi. Avian receptors were strongly present in the upper respiratory tract of the falcons, in accordance with the consistent oral viral shedding detected by RRT-PCR in both H5N1 HPAI and H7N2 LPAI infected falcons. The present study demonstrates that gyr-saker hybrid falcons are highly susceptible to H5N1 HPAI virus infection, as previously observed, and that they may play a major role in the spreading of both HPAI and LPAI viruses. For the first time in raptors, natural infection by feeding on infected prey was successfully reproduced. The use of avian prey species in falconry husbandry and wildlife rehabilitation facilities could put valuable birds

Highly (H5N1) and low (H7N2) pathogenic avian influenza virus infection in falcons via nasochoanal route and ingestion of experimentally infected prey.

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Bertran, Kateri; Busquets, Núria; Abad, Francesc Xavier; García de la Fuente, Jorge; Solanes, David; Cordón, Iván; Costa, Taiana; Dolz, Roser; Majó, Natàlia

2012-01-01

An experimental infection with highly pathogenic avian influenza (HPAI) and low pathogenic avian influenza (LPAI) viruses was carried out on falcons in order to examine the effects of these viruses in terms of pathogenesis, viral distribution in tissues and viral shedding. The distribution pattern of influenza virus receptors was also assessed. Captive-reared gyr-saker (Falco rusticolus x Falco cherrug) hybrid falcons were challenged with a HPAI H5N1 virus (A/Great crested grebe/Basque Country/06.03249/2006) or a LPAI H7N2 virus (A/Anas plathyrhynchos/Spain/1877/2009), both via the nasochoanal route and by ingestion of previously infected specific pathogen free chicks. Infected falcons exhibited similar infection dynamics despite the different routes of exposure, demonstrating the effectiveness of in vivo feeding route. H5N1 infected falcons died, or were euthanized, between 5-7 days post-infection (dpi) after showing acute severe neurological signs. Presence of viral antigen in several tissues was confirmed by immunohistochemistry and real time RT-PCR (RRT-PCR), which were generally associated with significant microscopical lesions, mostly in the brain. Neither clinical signs, nor histopathological findings were observed in any of the H7N2 LPAI infected falcons, although all of them had seroconverted by 11 dpi. Avian receptors were strongly present in the upper respiratory tract of the falcons, in accordance with the consistent oral viral shedding detected by RRT-PCR in both H5N1 HPAI and H7N2 LPAI infected falcons. The present study demonstrates that gyr-saker hybrid falcons are highly susceptible to H5N1 HPAI virus infection, as previously observed, and that they may play a major role in the spreading of both HPAI and LPAI viruses. For the first time in raptors, natural infection by feeding on infected prey was successfully reproduced. The use of avian prey species in falconry husbandry and wildlife rehabilitation facilities could put valuable birds of prey and

Changes in poultry handling behavior and poultry mortality reporting among rural Cambodians in areas affected by HPAI/H5N1.

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Maria D Van Kerkhove

2009-07-01

Full Text Available Since 2004, 21 highly pathogenic avian influenza H5N1 outbreaks in domestic poultry and eight human cases have been confirmed in Cambodia. As a result, a large number of avian influenza education campaigns have been ongoing in provinces in which H5N1outbreaks have occurred in humans and/or domestic poultry.Data were collected from 1,252 adults >15 years old living in two southern provinces in Cambodia where H5N1 has been confirmed in domestic poultry and human populations using two cross-sectional surveys conducted in January 2006 and in November/December 2007. Poultry handling behaviors, poultry mortality occurrence and self-reported notification of suspect H5N1 poultry cases to animal health officials in these two surveys were evaluated. Our results demonstrate that although some at risk practices have declined since the first study, risky contact with poultry is still frequent. Improved rates of reporting poultry mortality were observed overall, but reporting to trained village animal health workers decreased by approximately 50%.Although some improvements in human behavior have occurred, there are still areas--particularly with respect to the handling of poultry among children and the proper treatment of poultry and the surrounding household environment--that need to be addressed in public health campaigns. Though there were some differences in the sampling methods of the 2006 and 2007 surveys, our results illustrate the potential to induce considerable, potentially very relevant, behavioral changes over a short period of time.

Spatial and temporal patterns of global H5N1 outbreaks

CSIR Research Space (South Africa)

Si, YL

2008-07-01

Full Text Available -96. Walter, C., Mcbratney, A. B., Rossel, R. A. V. and Markus, J. A., 2005. Spatial point-process statistics: concepts and application to the analysis of lead contamination in urban soil. Environmetrics, 16, pp. 339-355. Ward, M. P., Maftei, D., Apostu... OF GLOBAL H5N1 OUTBREAKS Y.L. Si a,c, *, P. Debba b, A. K. Skidmore a, A. G. Toxopeus a, L. Li c a ITC, Department of Natural Resources, 7500AA Enschede, The Netherlands – (yali, skidmore, toxopeus)@itc.nl b Council for Scientific and Industrial...

Local amplification of highly pathogenic avian influenza H5N8 viruses in wild birds in the Netherlands, 2016 to 2017

NARCIS (Netherlands)

Poen, Marjolein J.; Bestebroer, Theo M.; Vuong, Oanh; Scheuer, Rachel D.; Jeugd, van der Henk P.; Kleyheeg, Erik; Eggink, Dirk; Lexmond, Pascal; Brand, van den Judith M.A.; Begeman, Lineke; Vliet, van der Stefan; Müskens, Gerhard J.D.M.; Majoor, Frank A.; Koopmans, Marion P.G.; Kuiken, Thijs; Fouchier, Ron A.M.

2018-01-01

Introduction: Highly pathogenic avian influenza (HPAI) viruses of subtype H5N8 were re-introduced into the Netherlands by late 2016, after detections in southeast Asia and Russia. This second H5N8 wave resulted in a large number of outbreaks in poultry farms and the deaths of large numbers of wild

Local amplification of highly pathogenic avian influenza H5N8 viruses in wild birds in the Netherlands, 2016 to 2017

NARCIS (Netherlands)

Poen, Marjolein J; Bestebroer, Theo M; Vuong, Oanh; Scheuer, Rachel D; van der Jeugd, Henk P; Kleyheeg, Erik; Eggink, Dirk; Lexmond, Pascal; van den Brand, Judith M A; Begeman, Lineke; van der Vliet, Stefan; Müskens, Gerhard J D M; Majoor, Frank A; Koopmans, Marion P G; Kuiken, Thijs; Fouchier, Ron A M

IntroductionHighly pathogenic avian influenza (HPAI) viruses of subtype H5N8 were re-introduced into the Netherlands by late 2016, after detections in south-east Asia and Russia. This second H5N8 wave resulted in a large number of outbreaks in poultry farms and the deaths of large numbers of wild

Risk factors for exposure to influenza a viruses, including subtype H5 viruses, in Thai free-grazing ducks.

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Beaudoin, A L; Kitikoon, P; Schreiner, P J; Singer, R S; Sasipreeyajan, J; Amonsin, A; Gramer, M R; Pakinsee, S; Bender, J B

2014-08-01

Free-grazing ducks (FGD) have been associated with highly pathogenic avian influenza (HPAI) H5N1 outbreaks and may be a viral reservoir. In July-August 2010, we assessed influenza exposure of Thai FGD and risk factors thereof. Serum from 6254 ducks was analysed with enzyme-linked immunosorbent assay (ELISA) to detect antibodies to influenza A nucleoprotein (NP), and haemagglutinin H5 protein. Eighty-five per cent (5305 ducks) were seropositive for influenza A. Of the NP-seropositive sera tested with H5 assays (n = 1423), 553 (39%) were H5 ELISA positive and 57 (4%) suspect. Twelve per cent (74 of 610) of H5 ELISA-positive/suspect ducks had H5 titres ≥ 1 : 20 by haemagglutination inhibition. Risk factors for influenza A seropositivity include older age, poultry contact, flock visitors and older purchase age. Study flocks had H5 virus exposure as recently as March 2010, but no HPAI H5N1 outbreaks have been identified in Thailand since 2008, highlighting a need for rigorous FGD surveillance. © 2012 Blackwell Verlag GmbH.

Spatio-Temporal Occurrence Modeling of Highly Pathogenic Avian Influenza Subtype H5N1: A Case Study in the Red River Delta, Vietnam

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Chinh C. Tran

2013-11-01

Full Text Available Highly Pathogenic Avian Influenza (HPAI subtype H5N1 poses severe threats to both animals and humans. Investigating where, when and why the disease occurs is important to help animal health authorities develop effective control policies. This study takes into account spatial and temporal occurrence of HPAI H5N1 in the Red River Delta of Vietnam. A two-stage procedure was used: (1 logistic regression modeling to identify and quantify factors influencing the occurrence of HPAI H5N1; and (2 a geostatistical approach to develop monthly predictive maps. The results demonstrated that higher average monthly temperatures and poultry density in combination with lower average monthly precipitation, humidity in low elevation areas, roughly from November to January and April to June, contribute to the higher occurrence of HPAI H5N1. Provinces near the Gulf of Tonkin, including Hai Phong, Hai Duong, Thai Binh, Nam Dinh and Ninh Binh are areas with higher probability of occurrence of HPAI H5N1.

The Influenza Virus and the 2009 H1N1 Outbreak

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2016-04-08

MDW/SGVU SUBJECT: Professional Presentation Approval 8 APR 2016 1. Your paper, entitled The Influenza Virus and the 2009 HlNl Outbreak presented at...L TO BE PUBLISHED OR PRESENTED The Influenza Virus and the 2009 H1N1 Outbreak 2. FUNDING RECEIVED FOR THIS STUDY? DYES [g] NO FUNDING SOURCE: I I...336:!. ~~ 2 C-; MARKE. COON. :vtajor. USAF Acting Chic!’. Civil I.aw The Influenza Virus and the 2009 H 1 N 1 Outbreak Thomas. F. Gibbons, Ph.D

Highly pathogenic avian influenza H5N1 in Mainland China

NARCIS (Netherlands)

X.-L. Li (Xin-Lou); K. Liu (Kun); H.-W. Yao (Hong-Wu); Y. Sun (Ye); W.-J. Chen (Wan-Jun); R.-X. Sun (Ruo-Xi); S.J. de Vlas (Sake); L.Q. Fang (Lily); W.-C. Cao (Wu-Chun)

2015-01-01

textabstractHighly pathogenic avian influenza (HPAI) H5N1 has posed a significant threat to both humans and birds, and it has spanned large geographic areas and various ecological systems throughout Asia, Europe and Africa, but especially in mainland China. Great efforts in control and prevention of

Suboptimal protection against H5N1 highly pathogenic avian influenza viruses from Vietnam in ducks vaccinated with commercial poultry vaccines.

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Cha, Ra Mi; Smith, Diane; Shepherd, Eric; Davis, C Todd; Donis, Ruben; Nguyen, Tung; Nguyen, Hoang Dang; Do, Hoa Thi; Inui, Ken; Suarez, David L; Swayne, David E; Pantin-Jackwood, Mary

2013-10-09

Domestic ducks are the second most abundant poultry species in many Asian countries including Vietnam, and play a critical role in the epizootiology of H5N1 highly pathogenic avian influenza (HPAI) [FAO]. In this study, we examined the protective efficacy in ducks of two commercial H5N1 vaccines widely used in Vietnam; Re-1 containing A/goose/Guangdong/1/1996 hemagglutinin (HA) clade 0 antigens, and Re-5 containing A/duck/Anhui/1/2006 HA clade 2.3.4 antigens. Ducks received two doses of either vaccine at 7 and at 14 or 21 days of age followed by challenge at 30 days of age with viruses belonging to the HA clades 1.1, 2.3.4.3, 2.3.2.1.A and 2.3.2.1.B isolated between 2008 and 2011 in Vietnam. Ducks vaccinated with the Re-1 vaccine were protected after infection with the two H5N1 HPAI viruses isolated in 2008 (HA clades 1.1 and 2.3.4.3) showing no mortality and limited virus shedding. The Re-1 and Re-5 vaccines conferred 90-100% protection against mortality after challenge with the 2010 H5N1 HPAI viruses (HA clade 2.3.2.1.A); but vaccinated ducks shed virus for more than 7 days after challenge. Similarly, the Re-1 and Re-5 vaccines only showed partial protection against the 2011 H5N1 HPAI viruses (HA clade 2.3.2.1.A and 2.3.2.1.B), with a high proportion of vaccinated ducks shedding virus for more than 10 days. Furthermore, 50% mortality was observed in ducks vaccinated with Re-1 and challenged with the 2.3.2.1.B virus. The HA proteins of the 2011 challenge viruses had the greatest number of amino acid differences from the two vaccines as compared to the viruses from 2008 and 2009, which correlates with the lesser protection observed with these viruses. These studies demonstrate the suboptimal protection conferred by the Re-1 and Re-5 commercial vaccines in ducks against H5N1 HPAI clade 2.3.2.1 viruses, and underscore the importance of monitoring vaccine efficacy in the control of H5N1 HPAI in ducks. Published by Elsevier Ltd.

Cross-protection against lethal H5N1 challenge ferrets with an adjuvanted pandemic influenza vaccine

NARCIS (Netherlands)

B. Baras (Benoît); K.J. Stittelaar (Koert); J.H. Simon (James); R.J.M.M. Thoolen (Robert); S.P. Mossman (Sally); F.H. Pistoor (Frank); G. van Amerongen (Geert); M.A. Wettendorff (Martine); E. Hanon (Emmanuel); A.D.M.E. Osterhaus (Albert)

2008-01-01

textabstractBackground. Unprecedented spread between birds and mammals of highly pathogenic avian influenza viruses (HPAI) of the H5N1 subtype has resulted in hundreds of human infections with a high fatality rate. This has highlighted the urgent need for the development of H5N1 vaccines that can be

Presence of serum antibodies to influenza A subtypes H5 and N1 in swans and ibises in French wetlands, irrespective of highly pathogenic H5N1 natural infection.

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Niqueux, Eric; Guionie, Olivier; Schmitz, Audrey; Hars, Jean; Jestin, Véronique

2010-03-01

Highly pathogenic (HP) avian influenza A viruses (AIVs) subtype H5N1 (subclade 2.2) were detected in wild birds during outbreaks in France during winter 2006 and summer 2007 in la Dombes wetlands (eastern France) and in Moselle wetlands (northeastern France), respectively. Blood samples from apparently healthy wild birds were collected in 2006 and 2007 from the end of the outbreak to several weeks after the influenza A outbreak inside and outside the contaminated areas, and in 2008 outside the contaminated areas. The samples were tested for the presence and/or quantitation of serum antibodies to influenza A subtypes H5 and N1 using hemagglutination inhibition tests (HITs), a commercial N1-specific enzyme-linked immunosorbent assay kit, and virus neutralization assay. In the HIT, low pathogenicity (LP) and HP H5 AIVs (belonging to H5N1, H5N2, and H5N3 subtypes) were used as antigens. One hundred mute swans were bled in the la Dombes outbreak area in 2006. During 2007, 46 mallards, 69 common pochards, and 59 mute swans were sampled in the Moselle outbreak area. For comparison, blood samples were also collected in 2007 from 60 mute swans from the Marne department where no HP H5N1 influenza A cases have been reported, and in 2008 from 111 sacred ibises in western France where no HP H5N1 influenza A infections in wild birds have been reported either. Mute swans (irrespective of their origin and time of sampling) and sacred ibises (from an area with no known outbreaks) had the highest prevalence of positive sera in the H5 HIT (49-69% and 64%, respectively). The prevalence of anti-H5 antibodies in mallards and common pochards was lower (28% and 27%, respectively). Positive H5- and N1-antibody responses were also significantly associated in swans (irrespective of their origin and time of sampling) and in sacred ibises. However, in swans from the area without outbreaks, the HIT titer against an H5N1 LPAIV was significantly higher than against an H5N1 2.2.1 HPAIV, whereas no

Immunity to current H5 highly pathogenic avian influenza viruses: From vaccines to adaptive immunity in wild birds

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Following the 2014-2015 outbreaks of H5N2 and H5N8 highly pathogenic avian influenza (HPAI) in the U.S., studies were performed to assess the immunity required for protection against future outbreaks should they occur. We assessed the ability of vaccines to induce protection of chickens and turkeys...

Highly pathogenic avian influenza virus subtype H5N1 in mute swans (Cygnus olor) in Central Bosnia.

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Goletić, Teufik; Gagić, Abdulah; Residbegović, Emina; Kustura, Aida; Kavazović, Aida; Savić, Vladimir; Harder, Timm; Starick, Elke; Prasović, Senad

2010-03-01

In order to determine the actual prevalence of avian influenza viruses (AIVs) in wild birds in Bosnia and Herzegovina, extensive surveillance was carried out between October 2005 and April 2006. A total of 394 samples representing 41 bird species were examined for the presence of influenza A virus using virus isolation in embryonated chicken eggs, PCR, and nucleotide sequencing. AIV subtype H5N1 was detected in two mute swans (Cygnus olor). The isolates were determined to be highly pathogenic avian influenza (HPAI) virus and the hemagglutinin sequence was closely similar to A/Cygnus olor/Astrakhan/ Ast05-2-10/2005 (H5N1). This is the first report of HPAI subtype H5N1 in Bosnia and Herzegovina.

A molecular and antigenic survey of H5N1 highly pathogenic avian influenza virus isolates from smallholder duck farms in Central Java, Indonesia during 2007-2008

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Junaidi Akhmad

2011-09-01

Full Text Available Abstract Background Indonesia is one of the countries most severely affected by H5N1 highly pathogenic avian influenza (HPAI virus in terms of poultry and human health. However, there is little information on the diversity of H5N1 viruses circulating in backyard farms, where chickens and ducks often intermingle. In this study, H5N1 virus infection occurring in 96 smallholder duck farms in central Java, Indonesia from 2007-2008 was investigated and the molecular and antigenic characteristics of H5N1 viruses isolated from these farms were analysed. Results All 84 characterised viruses belonged to H5N1 clade 2.1 with three virus sublineages being identified: clade 2.1.1 (1, clade 2.1.3 (80, and IDN/6/05-like viruses (3 that did not belong to any of the present clades. All three clades were found in ducks, while only clade 2.1.3 was isolated from chickens. There were no significant amino acid mutations of the hemagglutinin (HA and neuraminidase (NA sites of the viruses, including the receptor binding, glycosylation, antigenic and catalytic sites and NA inhibitor targets. All the viruses had polybasic amino acids at the HA cleavage site. No evidence of major antigenic variants was detected. Based on the HA gene, identical virus variants could be found on different farms across the study sites and multiple genetic variants could be isolated from HPAI outbreaks simultaneously or at different time points from single farms. HPAI virus was isolated from both ducks and chickens; however, the proportion of surviving duck cases was considerably higher than in chickens. Conclusions The 2.1.3 clade was the most common lineage found in this study. All the viruses had sequence characteristic of HPAI, but negligible variations in other recognized amino acids at the HA and NA proteins which determine virus phenotypes. Multiple genetic variants appeared to be circulating simultaneously within poultry communities. The high proportion of live duck cases compared to

A molecular and antigenic survey of H5N1 highly pathogenic avian influenza virus isolates from smallholder duck farms in Central Java, Indonesia during 2007-2008.

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Wibawa, Hendra; Henning, Joerg; Wong, Frank; Selleck, Paul; Junaidi, Akhmad; Bingham, John; Daniels, Peter; Meers, Joanne

2011-09-07

Indonesia is one of the countries most severely affected by H5N1 highly pathogenic avian influenza (HPAI) virus in terms of poultry and human health. However, there is little information on the diversity of H5N1 viruses circulating in backyard farms, where chickens and ducks often intermingle. In this study, H5N1 virus infection occurring in 96 smallholder duck farms in central Java, Indonesia from 2007-2008 was investigated and the molecular and antigenic characteristics of H5N1 viruses isolated from these farms were analysed. All 84 characterised viruses belonged to H5N1 clade 2.1 with three virus sublineages being identified: clade 2.1.1 (1), clade 2.1.3 (80), and IDN/6/05-like viruses (3) that did not belong to any of the present clades. All three clades were found in ducks, while only clade 2.1.3 was isolated from chickens. There were no significant amino acid mutations of the hemagglutinin (HA) and neuraminidase (NA) sites of the viruses, including the receptor binding, glycosylation, antigenic and catalytic sites and NA inhibitor targets. All the viruses had polybasic amino acids at the HA cleavage site. No evidence of major antigenic variants was detected. Based on the HA gene, identical virus variants could be found on different farms across the study sites and multiple genetic variants could be isolated from HPAI outbreaks simultaneously or at different time points from single farms. HPAI virus was isolated from both ducks and chickens; however, the proportion of surviving duck cases was considerably higher than in chickens. The 2.1.3 clade was the most common lineage found in this study. All the viruses had sequence characteristic of HPAI, but negligible variations in other recognized amino acids at the HA and NA proteins which determine virus phenotypes. Multiple genetic variants appeared to be circulating simultaneously within poultry communities. The high proportion of live duck cases compared to chickens over the study period suggests that ducks are

Detection of H5N1 high-pathogenicity avian influenza virus in meat and tracheal samples from experimentally infected chickens.

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Das, Amaresh; Spackman, Erica; Thomas, Colleen; Swayne, David E; Suarez, David L

2008-03-01

The Asian H5N1 highly pathogenic avian influenza (HPAI) virus causes a systemic disease with high mortality of poultry and is potentially zoonotic. In both chickens and ducks, the virus has been demonstrated to replicate in both cardiac and skeletal muscle cells. Experimentally, H5N1 HPAI virus has been transmitted to chickens through the consumption of raw infected meat. In this study, we investigated virus replication in cardiac and skeletal muscle and in the trachea of chickens after experimental intranasal inoculation with the H5N1 HPAI virus. The virus was detected in tissues by real-time reverse transcription-polymerase chain reaction (RRT-PCR) and virus isolation, and in the trachea by RRT-PCR and a commercial avian influenza (AI) viral antigen detection test. A modified RNA extraction protocol was developed for rapid detection of the virus in tissues by RRT-PCR. The H5N1 HPAI virus was sporadically detected in meat and the tracheas of infected birds without any clinical sign of disease as early as 6 hr postinfection (PI), and was detected in all samples tested at 24 hr PI and later. No differences in sensitivity were seen between virus isolation and RRT-PCR in meat samples. The AI viral antigen detection test on tracheal swabs was a useful method for identifying infected chickens when they were sick or dead, but was less sensitive in detecting infected birds when they were preclinical. This study provides data indicating that preslaughter tracheal swab testing can identify birds infected with HPAI among the daily mortality and prevent infected flocks from being sent to processing plants. In addition, the modified RNA extraction and RRT-PCR test on meat samples provide a rapid and sensitive method of identifying HPAI virus in illegal contraband or domestic meat samples.

Biosecurity and Circulation of Influenza A (H5N1) Virus in Live-Bird Markets in Bangladesh, 2012.

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Biswas, P K; Giasuddin, M; Nath, B K; Islam, M Z; Debnath, N C; Yamage, M

2017-06-01

Bangladesh has been considered as one of the five countries endemic with highly pathogenic avian influenza A subtype H5N1 (HPAI H5N1). Live-bird markets (LBMs) in south Asian countries are believed to play important roles in the transmission of HPAI H5N1 and others due to its central location as a hub of the poultry trading. Food and Agriculture Organization (FAO) of the United Nations has been promoting improved biosecurity in LBMs in Bangladesh. In 2012, by enrolling 32 large LBMs: 10 with FAO interventions and 22 without assistance, we assessed the virus circulation in the selected LBMs by applying standard procedures to investigate market floors, poultry stall floors, poultry-holding cases and slaughter areas and the overall biosecurity using a questionnaire-based survey. Relative risk (RR) was examined to compare the prevalence of HPAI H5N1 in the intervened and non-intervened LBMs. The measures practised in significantly more of the FAO-intervened LBMs included keeping of slaughter remnants in a closed container; decontamination of poultry vehicles at market place; prevention of crows' access to LBM, market/floor cleaning by market committee; wet cleaning; disinfection of floor/poultry stall after cleaning; and good supply of clean water at market (P Bangladesh regardless of interventions, albeit at lower levels than in other endemic countries. © 2015 Blackwell Verlag GmbH.

Immunomorphologic Manifestations in Mice Liver Infected with Influenza A/H5N1, A/Goose/Krasnoozerskoye/627/05 Strain

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Oxana V. Potapova

2013-01-01

Full Text Available Highly pathogenic avian influenza H5N1 (HPAI H5N1 viruses can infect mammals, including humans, causing severe systemic disease with the inhibition of the immune system and a high mortality rate. In conditions of lymphoid tissue depletion, the liver plays an important role in host defence against viruses. The changes in mice liver infected with HPAI H5N1 virus A/goose/Krasnoozerskoye/627/05 have been studied. It has been shown that the virus persistence in the liver leads to the expression of proinflammatory cytokines (TNF-α, IL-6 and intracellular proteases (lysozyme, cathepsin D, and myeloperoxidase by Kupffer cells. Defective antiviral response exacerbates destructive processes in the liver accelerating the development of liver failure.

Hemagglutinin pseudotyped lentiviral particles: characterization of a new method for avian H5N1 influenza sero-diagnosis.

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Nefkens , Isabelle; Garcia , Jean-Michel; Ling , Chu Shui; Lagarde , Nadège; Nicholls , John; Tang , Dong Jiang; Peiris , Malik; Buchy , Philippe; Altmeyer , Ralf

2007-01-01

BACKGROUND: Highly pathogenic avian influenza (HPAI) H5N1 has spread globally in birds and infected over 270 humans with an apparently high mortality rate. Serologic studies to determine the extent of asymptomatic H5N1 infection in humans and other mammals and to investigate the immunogenicity of current H5N1 vaccine candidates have been hampered by the biosafety requirements needed for H5N1 micro-neutralization tests. OBJECTIVE: Development of a serodiagnostic tool for highly pathogenic infl...

The response of mute swans (Cygnus olor, Gm. 1789) to vaccination against avian influenza with an inactivated H5N2 vaccine.

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Dolka, Beata; Żbikowski, Artur; Dolka, Izabella; Szeleszczuk, Piotr

2016-10-22

Recent epidemics of highly pathogenic avian influenza (HPAI) produced an unprecedented number of cases in mute swans (Cygnus olor) in European countries, which indicates that these birds are very sensitive to the H5N1 virus. The HPAI outbreaks stirred a debate on the controversial stamping-out policy in populations of protected bird species. After preventive vaccination had been approved in the European Union, several countries have introduced vaccination schemes to protect poultry, captive wild birds or exotic birds in zoos against HPAI. The aim of this study was to investigate the immune response of wild mute swans to immunization with an inactivated AI H5N2 vaccine approved for use in poultry. The serological responses of mute swans were assessed by comparison with racing pigeons (Columba livia), a species which is characterized by different susceptibility to infection with the H5N1 HPAI virus and plays a questionable role in the ecology of influenza (H5N1) viruses. Swans were vaccinated once or twice at an interval of 4 weeks. The humoral immune response was evaluated by hemagglutination inhibition (HI) and NP-ELISA. The lymphocyte blast transformation test was used to determine the cell-mediated immune response. Higher values of the geometric mean titer (GMT) and 100 % seroconversion (HI ≥32) were noted in double vaccinated swans (1448.2) than in single vaccinated swans (128.0) or in double vaccinated pigeons (215.3). Significant differences in HI titers were observed between swans and pigeons, but no variations in ELISA scores were noted after the booster dose. Immunization of swans had no effect on the proliferative activity of lymphocytes. The inactivated H5N2 vaccine was safe and immunogenic for mute swans and pigeons. Vaccination may have practical implications for swans kept in zoos, wildlife parks or rehabilitation centers. However, challenge studies are needed to prove the efficacy of the H5N2 AI vaccine.

An M2e-based multiple antigenic peptide vaccine protects mice from lethal challenge with divergent H5N1 influenza viruses

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Chan Chris CS

2010-01-01

Full Text Available Abstract Background A growing concern has raised regarding the pandemic potential of the highly pathogenic avian influenza (HPAI H5N1 viruses. Consequently, there is an urgent need to develop an effective and safe vaccine against the divergent H5N1 influenza viruses. In the present study, we designed a tetra-branched multiple antigenic peptide (MAP-based vaccine, designated M2e-MAP, which contains the sequence overlapping the highly conserved extracellular domain of matrix protein 2 (M2e of a HPAI H5N1 virus, and investigated its immune responses and cross-protection against different clades of H5N1 viruses. Results Our results showed that M2e-MAP vaccine induced strong M2e-specific IgG antibody responses following 3-dose immunization of mice with M2e-MAP in the presence of Freunds' or aluminium (alum adjuvant. M2e-MAP vaccination limited viral replication and attenuated histopathological damage in the challenged mouse lungs. The M2e-MAP-based vaccine protected immunized mice against both clade1: VN/1194 and clade2.3.4: SZ/406H H5N1 virus challenge, being able to counteract weight lost and elevate survival rate following lethal challenge of H5N1 viruses. Conclusions These results suggest that M2e-MAP presenting M2e of H5N1 virus has a great potential to be developed into an effective subunit vaccine for the prevention of infection by a broad spectrum of HPAI H5N1 viruses.

Potential spread of highly pathogenic avian influenza H5N1 by wildfowl: dispersal ranges and rates determined from large-scale satellite telemetry

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Gaidet, Nicolas; Cappelle, Julien; Takekawa, John Y.; Prosser, Diann J.; Iverson, Samuel A.; Douglas, David C.; Perry, William M.; Mundkur, Taej; Newman, Scott H.

2010-01-01

1. Migratory birds are major candidates for long-distance dispersal of zoonotic pathogens. In recent years, wildfowl have been suspected of contributing to the rapid geographic spread of the highly pathogenic avian influenza (HPAI) H5N1 virus. Experimental infection studies reveal that some wild ducks, geese and swans shed this virus asymptomatically and hence have the potential to spread it as they move. 2. We evaluate the dispersive potential of HPAI H5N1 viruses by wildfowl through an analysis of the movement range and movement rate of birds monitored by satellite telemetry in relation to the apparent asymptomatic infection duration (AID) measured in experimental studies. We analysed the first large-scale data set of wildfowl movements, including 228 birds from 19 species monitored by satellite telemetry in 2006–2009, over HPAI H5N1 affected regions of Asia, Europe and Africa. 3. Our results indicate that individual migratory wildfowl have the potential to disperse HPAI H5N1 over extensive distances, being able to perform movements of up to 2900 km within timeframes compatible with the duration of asymptomatic infection. 4. However, the likelihood of such virus dispersal over long distances by individual wildfowl is low: we estimate that for an individual migratory bird there are, on average, only 5–15 days per year when infection could result in the dispersal of HPAI H5N1 virus over 500 km. 5. Staging at stopover sites during migration is typically longer than the period of infection and viral shedding, preventing birds from dispersing a virus over several consecutive but interrupted long-distance movements. Intercontinental virus dispersion would therefore probably require relay transmission between a series of successively infected migratory birds. 6. Synthesis and applications. Our results provide a detailed quantitative assessment of the dispersive potential of HPAI H5N1 virus by selected migratory birds. Such dispersive potential rests on the

Pathogenesis of highly pathogenic avian influenza A/turkey/Turkey/1/2005 H5N1 in Pekin ducks (Anas platyrhynchos) infected experimentally.

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Löndt, Brandon Z; Nunez, Alejandro; Banks, Jill; Nili, Hassan; Johnson, Linda K; Alexander, Dennis J

2008-12-01

Asian H5N1 (hereafter referred to as panzootic H5N1) highly pathogenic avian influenza (HPAI) virus has caused large numbers of deaths in both poultry and wild-bird populations. Recent isolates of this virus have been reported to cause disease and death in commercial ducks, which has not been seen with other HPAI viruses. However, little is known about either the dissemination of this H5N1 within the organs or the cause of death in infected ducks. Nineteen 4-week-old Pekin ducks were infected with 10(6.7) median egg infectious doses of HPAI A/turkey/Turkey/1/05 (H5N1, clade 2.2) in 0.1ml via the intranasal and intraocular routes. Cloacal and oropharyngeal swabs were taken daily before three animals were selected randomly and killed humanely for postmortem examination, when samples of tissues were taken for real-time reverse transcriptase-polymerase chain reaction, histopathological examination and immunohistochemistry. Clinical signs were first observed 4 days post infection (d.p.i.) and included depression, reluctance to feed, in-coordination and torticollis resulting in the death of all the birds remaining on 5d.p.i. Higher levels of virus shedding were detected from oropharyngeal swabs than from cloacal swabs. Real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry identified peak levels of virus at 2d.p.i. in several organs. In the spleen, lung, kidney, caecal tonsils, breast muscle and thigh muscle the levels were greatly reduced at 3d.p.i. However, the highest viral loads were detected in the heart and brain from 3d.p.i. and coincided with the appearance of clinical signs and death. Our experimental results demonstrate the systemic spread of this HPAI H5N1 virus in Pekin ducks, and the localization of virus in the brain and heart tissue preceding death.

Prophylactic and therapeutic efficacy of human monoclonal antibodies against H5N1 influenza.

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Cameron P Simmons

2007-05-01

Full Text Available New prophylactic and therapeutic strategies to combat human infections with highly pathogenic avian influenza (HPAI H5N1 viruses are needed. We generated neutralizing anti-H5N1 human monoclonal antibodies (mAbs and tested their efficacy for prophylaxis and therapy in a murine model of infection.Using Epstein-Barr virus we immortalized memory B cells from Vietnamese adults who had recovered from infections with HPAI H5N1 viruses. Supernatants from B cell lines were screened in a virus neutralization assay. B cell lines secreting neutralizing antibodies were cloned and the mAbs purified. The cross-reactivity of these antibodies for different strains of H5N1 was tested in vitro by neutralization assays, and their prophylactic and therapeutic efficacy in vivo was tested in mice. In vitro, mAbs FLA3.14 and FLD20.19 neutralized both Clade I and Clade II H5N1 viruses, whilst FLA5.10 and FLD21.140 neutralized Clade I viruses only. In vivo, FLA3.14 and FLA5.10 conferred protection from lethality in mice challenged with A/Vietnam/1203/04 (H5N1 in a dose-dependent manner. mAb prophylaxis provided a statistically significant reduction in pulmonary virus titer, reduced associated inflammation in the lungs, and restricted extrapulmonary dissemination of the virus. Therapeutic doses of FLA3.14, FLA5.10, FLD20.19, and FLD21.140 provided robust protection from lethality at least up to 72 h postinfection with A/Vietnam/1203/04 (H5N1. mAbs FLA3.14, FLD21.140 and FLD20.19, but not FLA5.10, were also therapeutically active in vivo against the Clade II virus A/Indonesia/5/2005 (H5N1.These studies provide proof of concept that fully human mAbs with neutralizing activity can be rapidly generated from the peripheral blood of convalescent patients and that these mAbs are effective for the prevention and treatment of H5N1 infection in a mouse model. A panel of neutralizing, cross-reactive mAbs might be useful for prophylaxis or adjunctive treatment of human cases of H5N1

Quantitative assessment of a spatial multicriteria model for highly pathogenic avian influenza H5N1 in Thailand, and application in Cambodia

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Paul, Mathilde C.; Goutard, Flavie L.; Roulleau, Floriane; Holl, Davun; Thanapongtharm, Weerapong; Roger, François L.; Tran, Annelise

2016-01-01

The Highly Pathogenic Avian Influenza H5N1 (HPAI) virus is now considered endemic in several Asian countries. In Cambodia, the virus has been circulating in the poultry population since 2004, with a dramatic effect on farmers’ livelihoods and public health. In Thailand, surveillance and control are still important to prevent any new H5N1 incursion. Risk mapping can contribute effectively to disease surveillance and control systems, but is a very challenging task in the absence of reliable disease data. In this work, we used spatial multicriteria decision analysis (MCDA) to produce risk maps for HPAI H5N1 in poultry. We aimed to i) evaluate the performance of the MCDA approach to predict areas suitable for H5N1 based on a dataset from Thailand, comparing the predictive capacities of two sources of a priori knowledge (literature and experts), and ii) apply the best method to produce a risk map for H5N1 in poultry in Cambodia. Our results showed that the expert-based model had a very high predictive capacity in Thailand (AUC = 0.97). Applied in Cambodia, MCDA mapping made it possible to identify hotspots suitable for HPAI H5N1 in the Tonlé Sap watershed, around the cities of Battambang and Kampong Cham, and along the Vietnamese border. PMID:27489997

Avian Influenza A(H5N1) Virus Outbreak Investigation: Application of the FAO-OIE-WHO Four-way Linking Framework in Indonesia.

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Setiawaty, V; Dharmayanti, N L P I; Misriyah; Pawestri, H A; Azhar, M; Tallis, G; Schoonman, L; Samaan, G

2015-08-01

WHO, FAO and OIE developed a 'four-way linking' framework to enhance the cross-sectoral sharing of epidemiological and virological information in responding to zoonotic disease outbreaks. In Indonesia, outbreak response challenges include completeness of data shared between human and animal health authorities. The four-way linking framework (human health laboratory/epidemiology and animal health laboratory/epidemiology) was applied in the investigation of the 193 rd human case of avian influenza A(H5N1) virus infection. As recommended by the framework, outbreak investigation and risk assessment findings were shared. On 18 June 2013, a hospital in West Java Province reported a suspect H5N1 case in a 2-year-old male. The case was laboratory-confirmed that evening, and the information was immediately shared with the Ministry of Agriculture. The human health epidemiology/laboratory team investigated the outbreak and conducted an initial risk assessment on 19 June. The likelihood of secondary cases was deemed low as none of the case contacts were sick. By 3 July, no secondary cases associated with the outbreak were identified. The animal health epidemiology/laboratory investigation was conducted on 19-25 June and found that a live bird market visited by the case was positive for H5N1 virus. Once both human and market virus isolates were sequenced, a second risk assessment was conducted jointly by the human health and animal health epidemiology/laboratory teams. This assessment concluded that the likelihood of additional human cases associated with this outbreak was low but that future sporadic human infections could not be ruled out because of challenges in controlling H5N1 virus contamination in markets. Findings from the outbreak investigation and risk assessments were shared with stakeholders at both Ministries. The four-way linking framework clarified the type of data to be shared. Both human health and animal health teams made ample data available, and there was

Antibody titer has positive predictive value for vaccine protection against challenge with natural antigenic-drift variants of H5N1 high-pathogenicity avian influenza viruses from Indonesia

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Beginning with Hong Kong in 2002, vaccines have been used as part of an integrated control strategy in 14 countries/regions to protect poultry against H5N1 high pathogenicity avian influenza (HPAI). H5N1 HPAI was first reported in Indonesia in 2003 and vaccination was initiated the following year. ...

Structural and antigenic variation among diverse clade 2 H5N1 viruses.

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David A Shore

Full Text Available Antigenic variation among circulating H5N1 highly pathogenic avian influenza A viruses mandates the continuous production of strain-specific pre-pandemic vaccine candidates and represents a significant challenge for pandemic preparedness. Here we assessed the structural, antigenic and receptor-binding properties of three H5N1 HPAI virus hemagglutinins, which were recently selected by the WHO as vaccine candidates [A/Egypt/N03072/2010 (Egypt10, clade 2.2.1, A/Hubei/1/2010 (Hubei10, clade 2.3.2.1 and A/Anhui/1/2005 (Anhui05, clade 2.3.4]. These analyses revealed that antigenic diversity among these three isolates was restricted to changes in the size and charge of amino acid side chains at a handful of positions, spatially equivalent to the antigenic sites identified in H1 subtype viruses circulating among humans. All three of the H5N1 viruses analyzed in this study were responsible for fatal human infections, with the most recently-isolated strains, Hubei10 and Egypt10, containing multiple residues in the receptor-binding site of the HA, which were suspected to enhance mammalian transmission. However, glycan-binding analyses demonstrated a lack of binding to human α2-6-linked sialic acid receptor analogs for all three HAs, reinforcing the notion that receptor-binding specificity contributes only partially to transmissibility and pathogenesis of HPAI viruses and suggesting that changes in host specificity must be interpreted in the context of the host and environmental factors, as well as the virus as a whole. Together, our data reveal structural linkages with phylogenetic and antigenic analyses of recently emerged H5N1 virus clades and should assist in interpreting the significance of future changes in antigenic and receptor-binding properties.

Lethal infection by a novel reassortant H5N1 avian influenza A virus in a zoo-housed tiger.

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He, Shang; Shi, Jianzhong; Qi, Xian; Huang, Guoqing; Chen, Hualan; Lu, Chengping

2015-01-01

In early 2013, a Bengal tiger (Panthera tigris) in a zoo died of respiratory distress. All specimens from the tiger were positive for HPAI H5N1, which were detected by real-time PCR, including nose swab, throat swab, tracheal swab, heart, liver, spleen, lung, kidney, aquae pericardii and cerebrospinal fluid. One stain of virus, A/Tiger/JS/1/2013, was isolated from the lung sample. Pathogenicity experiments showed that the isolate was able to replicate and cause death in mice. Phylogenetic analysis indicated that HA and NA of A/Tiger/JS/1/2013 clustered with A/duck/Vietnam/OIE-2202/2012 (H5N1), which belongs to clade 2.3.2.1. Interestingly, the gene segment PB2 shared 98% homology with A/wild duck/Korea/CSM-28/20/2010 (H4N6), which suggested that A/Tiger/JS/1/2013 is a novel reassortant H5N1 subtype virus. Immunohistochemical analysis also confirmed that the tiger was infected by this new reassortant HPAI H5N1 virus. Overall, our results showed that this Bengal tiger was infected by a novel reassortant H5N1, suggesting that the H5N1 virus can successfully cross species barriers from avian to mammal through reassortment. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Comparing introduction to Europe of highly pathogenic avian influenza viruses A(H5N8) in 2014 and A(H5N1) in 2005.

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Adlhoch, C; Gossner, C; Koch, G; Brown, I; Bouwstra, R; Verdonck, F; Penttinen, P; Harder, T

2014-12-18

Since the beginning of November 2014, nine outbreaks of highly pathogenic avian influenza virus (HPAIV) A(H5N8) in poultry have been detected in four European countries. In this report, similarities and differences between the modes of introduction of HPAIV A(H5N1) and A(H5N8) into Europe are described. Experiences from outbreaks of A(H5N1) in Europe demonstrated that early detection to control HPAIV in poultry has proven pivotal to minimise the risk of zoonotic transmission and prevention of human cases.

Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells

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Yuen Kit M

2009-10-01

Full Text Available Abstract Background Highly pathogenic avian influenza (HPAI H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease. Aim To study influenza A (H5N1 virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease. Methods We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces. Results We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our

Two aircraft carriers’ perspectives: a comparative of control measures in shipboard H1N1 outbreaks.

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Harwood, Jared L; LaVan, Joseph T; Brand, George J

2013-02-01

The USS George Washington (GW) and the USS Ronald Reagan (RR), 2 US Navy aircraft carriers, experienced almost simultaneous outbreaks of novel H1N1 influenza A in the summer of 2009. We compared the respective epidemic control measures taken and subsequent lessons learned. Data were collated from both outbreaks to assess various elements including attack rate, isolation/quarantine protocols, and treatment methods. The respective duration of each outbreak was compared with survival curve analysis. The number of personnel affected in each outbreak was compared using χ2 analysis. Differences were found in the protocols used on the 2 ships. The GW treated about two-thirds of the patients with oseltamivir through day 14 and quarantined all patients meeting case definition throughout the outbreak. Face masks were used throughout. The RR used oseltamivir and quarantined many fewer patients (through days 5 and 3, respectively). No face masks were used after day 5. The outbreaks were similar in duration (GW = 25 days, RR = 27 days, P = .38), but the RR had significantly more cases (n = 253 vs 142, P < .0001). A portion of each group had samples that were confirmed H1N1 by polymerase chain reaction. GW's protocol, including aggressive oseltamivir treatment of two-thirds of the cases and quarantine throughout the duration decreased the overall number of personnel affected, likely reducing the overall control reproduction number. Both outbreaks were similar in duration. Even though the GW expended significantly more resources than the RR, if the 2009 pandemic H1N1 strain had been as clinically severe as the 1918 pandemic, a more stringent treatment protocol may have been the only way to prevent significant operational impact.

Principles for vaccine protection in chickens and domestic waterfowl against avian influenza: emphasis on Asian H5N1 high pathogenicity avian influenza.

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Swayne, David E

2006-10-01

The H5N1 highly pathogenic (HP) avian influenza (AI) epizootic began with reports of mortality from China in 1996 and, by June 2005, caused outbreaks of disease in nine additional Asian countries, affecting or resulting in culling of over 200 million birds. Vaccines can be used in programs to prevent, manage, or eradicate AI. However, vaccines should only be used as part of a comprehensive control strategy that also includes biosecurity, quarantine, surveillance and diagnostics, education, and elimination of infected poultry. Potent AI vaccines, when properly used, can prevent disease and death, increase resistance to infection, reduce field virus replication and shedding, and reduce virus transmission, but do not provide "sterilizing immunity" in the field; i.e., vaccination does not completely prevent AI virus replication. Inactivated AI vaccines and a recombinant fowlpox-H5-AI vaccine are licensed and used in various countries. Vaccines have been shown to protect chickens, geese, and ducks from H5 HPAI. The inactivated vaccines prevented disease and mortality in chickens and geese, and reduced the ability of the field virus to replicate in gastrointestinal and respiratory tracts. Although the Asian H5N1 HPAI virus did not cause disease or mortality in ducks, the use of inactivated vaccine did reduce field virus replication in the respiratory and intestinal tracts. The inactivated vaccine protected geese from morbidity and mortality, and reduced challenge virus replication. The recombinant fowlpox-H5-AI vaccine has provided similar protection, but the vaccine is used only in chickens and with the advantage of application at 1 day of age in the hatchery.

Geographical and Historical Patterns in the Emergences of Novel Highly Pathogenic Avian Influenza (HPAI H5 and H7 Viruses in Poultry

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Madhur S. Dhingra

2018-06-01

Full Text Available Over the years, the emergence of novel H5 and H7 highly pathogenic avian influenza viruses (HPAI has been taking place through two main mechanisms: first, the conversion of a low pathogenic into a highly pathogenic virus, and second, the reassortment between different genetic segments of low and highly pathogenic viruses already in circulation. We investigated and summarized the literature on emerging HPAI H5 and H7 viruses with the aim of building a spatio-temporal database of all these recorded conversions and reassortments events. We subsequently mapped the spatio-temporal distribution of known emergence events, as well as the species and production systems that they were associated with, the aim being to establish their main characteristics. From 1959 onwards, we identified a total of 39 independent H7 and H5 LPAI to HPAI conversion events. All but two of these events were reported in commercial poultry production systems, and a majority of these events took place in high-income countries. In contrast, a total of 127 reassortments have been reported from 1983 to 2015, which predominantly took place in countries with poultry production systems transitioning from backyard to intensive production systems. Those systems are characterized by several co-circulating viruses, multiple host species, regular contact points in live bird markets, limited biosecurity within value chains, and frequent vaccination campaigns that impose selection pressures for emergence of novel reassortants. We conclude that novel HPAI emergences by these two mechanisms occur in different ecological niches, with different viral, environmental and host associated factors, which has implications in early detection and management and mitigation of the risk of emergence of novel HPAI viruses.

Pathology of whooper swans (Cygnus cygnus) infected with H5N1 avian influenza virus in Akita, Japan, in 2008.

Science.gov (United States)

Ogawa, Shuji; Yamamoto, Yu; Yamada, Manabu; Mase, Masaji; Nakamura, Kikuyasu

2009-10-01

Two (1 adult and 1 young bird) of 4 H5N1-highly-pathogenic-avian-influenza (HPAI)-virus-infected whooper swans in Akita, Japan, in 2008 were investigated pathologically. Macroscopically, white spots with hemorrhages were scattered in the pancreas in the adult bird. Histologically, the adult bird had severe necrotizing pancreatitis and mild nonpurulent encephalitis. The young bird had severe nonpurulent encephalitis and nonpurulent enteric ganglionitis, and intestinal venous wall thickening. Virus antigens were detected in the lesions of pancreatitis in the adult bird and of encephalitis in adult and young birds. These findings suggest that the swans died or became moribund due to neurological disorders and necrotizing pancreatitis caused by H5N1 HPAI virus infection.

Genetic Characterization of Continually Evolving Highly Pathogenic H5N6 Influenza Viruses in China, 2012-2016.

Science.gov (United States)

Li, Meng; Zhao, Na; Luo, Jing; Li, Yuan; Chen, Lin; Ma, Jiajun; Zhao, Lin; Yuan, Guohui; Wang, Chengmin; Wang, Yutian; Liu, Yanhua; He, Hongxuan

2017-01-01

H5N6 is a highly pathogenic avian influenza (HPAI) and a zoonotic disease that causes recurring endemics in East Asia. At least 155 H5N6 outbreaks, including 15 human infections, have been reported in China. These repeated outbreaks have increased concern that the H5N6 virus may cross over to humans and cause a pandemic. In February, 2016, peafowls in a breeding farm exhibited a highly contagious disease. Post-mortem examinations, including RT-PCR, and virus isolation, confirmed that the highly pathogenic H5N6 influenza virus was the causative agent, and the strain was named A/ Pavo Cristatus /Jiangxi/JA1/2016. In animal experiments, it exhibited high pathogenicity in chickens and an estimated median lethal dose in mice of ~10 4.3 TCID 50 . A phylogenetic analysis showed that JA1/2016 was clustered in H5 clade 2.3.4.4. FG594-like H5N6 virus from Guangdong Province was the probable predecessor of JA1/2016, and the estimated divergence time was June 2014. Furthermore, we found that H5N6 influenza viruses can be classified into the two following groups: Group 1 and Group 2. Group 2 influenza viruses have not been detected since the end of 2014, whereas Group 1 influenza viruses have continually evolved and reassorted with the "gene pool" circulating in south China, resulting in the rise of novel subtypes of this influenza virus. An increase in the number of its identified hosts, the expanding range of its distribution, and the continual evolution of H5N6 AIVs enhance the risk that an H5N6 virus may spread to other continents and cause a pandemic.

Differences in the detection of highly pathogenic avian influenza H5N1 virus in feather samples from 4-week-old and 24-week-old infected Pekin ducks (Anas platyrhynchos var. domestica).

Science.gov (United States)

Aiello, Roberta; Beato, Maria Serena; Mancin, Marzia; Rigoni, Michela; Tejeda, Aurora Romero; Maniero, Silvia; Capua, Ilaria; Terregino, Calogero

2013-08-30

Previous studies have reported the detection of H5N1 HPAI virus in feathers from ducks naturally and experimentally infected and suggested that feather calami (FC) could be used as diagnostic samples for the early detection of H5N1 HPAI infections. Ducks are readily infected with H5N1 HPAI viruses although the development of clinical signs and deaths were reported as age-related with younger birds being more susceptible. The correlation between age and virus localisation in FC of infected ducks has not been studied to date. In the present study juvenile (4-week-old) and adult (24-week-old) Pekin ducks (Anas platyrhynchos var. domestica) were infected experimentally with a clade 2.2 H5N1 HPAI virus (A/duck/Nigeria/1071-23/2007). Tracheal (Tr) and cloacal (Cl) swabs and FC were collected at 3, 5, 7 and 10 days post infection and tested by RRT-PCR and a double antibody sandwich-ELISA (DAS-ELISA) developed in house. Virus was detected in swabs and FC of challenged ducks with a higher rate of detection in juvenile ducks. In this age group virus was detected over a longer period of time in FC compared to swabs. Our study showed that FC samples collected from young ducks are a valid diagnostic specimen for H5N1 HPAI virus detection. The DAS-ELISA on FC proved to be a suitable alternative diagnostic test when molecular and/or virus isolation techniques are not available therefore it could be useful in the diagnosis of H5N1 HPAI infections in under-resourced countries. Copyright © 2013 Elsevier B.V. All rights reserved.

Rivers and flooded areas identified by medium-resolution remote sensing improve risk prediction of the highly pathogenic avian influenza H5N1 in Thailand

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Weerapong Thanapongtharm

2013-11-01

Full Text Available Thailand experienced several epidemic waves of the highly pathogenic avian influenza (HPAI H5N1 between 2004 and 2005. This study investigated the role of water in the landscape, which has not been previously assessed because of a lack of high-resolution information on the distribution of flooded land at the time of the epidemic. Nine Landsat 7- Enhanced Thematic Mapper Plus scenes covering 174,610 km2 were processed using k-means unsupervised classification to map the distribution of flooded areas as well as permanent lakes and reservoirs at the time of the main epidemic HPAI H5N1 wave of October 2004. These variables, together with other factors previously identified as significantly associated with risk, were entered into an autologistic regression model in order to quantify the gain in risk explanation over previously published models. We found that, in addition to other factors previously identified as associated with risk, the proportion of land covered by flooding along with expansion of rivers and streams, derived from an existing, sub-district level (administrative level no. 3 geographical information system database, was a highly significant risk factor in this 2004 HPAI epidemic. These results suggest that water-borne transmission could have partly contributed to the spread of HPAI H5N1 during the epidemic. Future work stemming from these results should involve studies where the actual distribution of small canals, rivers, ponds, rice paddy fields and farms are mapped and tested against farm-level data with respect to HPAI H5N1.

Impact of the implementation of rest days in live bird markets on the dynamics of H5N1 highly pathogenic avian influenza.

Science.gov (United States)

Fournié, G; Guitian, F J; Mangtani, P; Ghani, A C

2011-08-07

Live bird markets (LBMs) act as a network 'hub' and potential reservoir of infection for domestic poultry. They may therefore be responsible for sustaining H5N1 highly pathogenic avian influenza (HPAI) virus circulation within the poultry sector, and thus a suitable target for implementing control strategies. We developed a stochastic transmission model to understand how market functioning impacts on the transmission dynamics. We then investigated the potential for rest days-periods during which markets are emptied and disinfected-to modulate the dynamics of H5N1 HPAI within the poultry sector using a stochastic meta-population model. Our results suggest that under plausible parameter scenarios, HPAI H5N1 could be sustained silently within LBMs with the time spent by poultry in markets and the frequency of introduction of new susceptible birds' dominant factors determining sustained silent spread. Compared with interventions applied in farms (i.e. stamping out, vaccination), our model shows that frequent rest days are an effective means to reduce HPAI transmission. Furthermore, our model predicts that full market closure would be only slightly more effective than rest days to reduce transmission. Strategies applied within markets could thus help to control transmission of the disease.

The highly pathogenic avian influenza A (H7N7) virus epidemic in the Netherlands in 2003 - lessons learned from the first five outbreaks

NARCIS (Netherlands)

Elbers, A.R.W.; Fabri, T.; Vries, T.S.; Wit, de J.J.; Pijpers, A.; Koch, G.

2004-01-01

Clinical signs and gross lesions observed in poultry submitted for postmortem examination (PME) from the first five infected poultry flocks preceding the detection of the primary outbreak of highly pathogenic avian influenza (HPAI) of subtype H7N7 during the 2003 epidemic in the Netherlands are

Host-specific exposure and fatal neurologic disease in wild raptors from highly pathogenic avian influenza virus H5N1 during the 2006 outbreak in Germany

NARCIS (Netherlands)

J.M.A. van den Brand (Judith); O. Krone (Oliver); P.U. Wolf (Peter U.); M.W.G. van de Bildt (Marco); G. van Amerongen (Geert); A.D.M.E. Osterhaus (Albert); T. Kuiken (Thijs)

2015-01-01

textabstractRaptors may contract highly pathogenic avian influenza virus H5N1 by hunting or scavenging infected prey. However, natural H5N1 infection in raptors is rarely reported. Therefore, we tested raptors found dead during an H5N1 outbreak in wild waterbirds in Mecklenburg-Western Pomerania,

Physician's knowledge, attitudes, and practices regarding seasonal influenza, pandemic influenza, and highly pathogenic avian influenza A (H5N1) virus infections of humans in Indonesia

OpenAIRE

Mangiri, Amalya; Iuliano, A. Danielle; Wahyuningrum, Yunita; Praptiningsih, Catharina Y.; Lafond, Kathryn E.; Storms, Aaron D.; Samaan, Gina; Ariawan, Iwan; Soeharno, Nugroho; Kreslake, Jennifer M.; Storey, J. Douglas; Uyeki, Timothy M.

2016-01-01

Indonesia has reported highest number of fatal human cases of highly pathogenic avian influenza (HPAI) A (H5N1) virus infection worldwide since 2005. There are limited data available on seasonal and pandemic influenza in Indonesia. During 2012, we conducted a survey of clinicians in two districts in western Java, Indonesia, to assess knowledge, attitudes, and practices (KAP) of clinical diagnosis, testing, and treatment of patients with seasonal influenza, pandemic influenza, or HPAI H5N1 vir...

Evolution of highly pathogenic H5N1 avian influenza viruses in Vietnam between 2001 and 2007.

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Xiu-Feng Wan

Full Text Available Highly pathogenic avian influenza (HPAI H5N1 viruses have caused dramatic economic losses to the poultry industry of Vietnam and continue to pose a serious threat to public health. As of June 2008, Vietnam had reported nearly one third of worldwide laboratory confirmed human H5N1 infections. To better understand the emergence, spread and evolution of H5N1 in Vietnam we studied over 300 H5N1 avian influenza viruses isolated from Vietnam since their first detection in 2001. Our phylogenetic analyses indicated that six genetically distinct H5N1 viruses were introduced into Vietnam during the past seven years. The H5N1 lineage that evolved following the introduction in 2003 of the A/duck/Hong Kong/821/2002-like viruses, with clade 1 hemagglutinin (HA, continued to predominate in southern Vietnam as of May 2007. A virus with a clade 2.3.4 HA newly introduced into northern Vietnam in 2007, reassorted with pre-existing clade 1 viruses, resulting in the emergence of novel genotypes with neuraminidase (NA and/or internal gene segments from clade 1 viruses. A total of nine distinct genotypes have been present in Vietnam since 2001, including five that were circulating in 2007. At least four of these genotypes appear to have originated in Vietnam and represent novel H5N1 viruses not reported elsewhere. Geographic and temporal analyses of H5N1 infection dynamics in poultry suggest that the majority of viruses containing new genes were first detected in northern Vietnam and subsequently spread to southern Vietnam after reassorting with pre-existing local viruses in northern Vietnam. Although the routes of entry and spread of H5N1 in Vietnam remain speculative, enhanced poultry import controls and virologic surveillance efforts may help curb the entry and spread of new HPAI viral genes.

Genetic Characterization of Continually Evolving Highly Pathogenic H5N6 Influenza Viruses in China, 2012–2016

Science.gov (United States)

Li, Meng; Zhao, Na; Luo, Jing; Li, Yuan; Chen, Lin; Ma, Jiajun; Zhao, Lin; Yuan, Guohui; Wang, Chengmin; Wang, Yutian; Liu, Yanhua; He, Hongxuan

2017-01-01

H5N6 is a highly pathogenic avian influenza (HPAI) and a zoonotic disease that causes recurring endemics in East Asia. At least 155 H5N6 outbreaks, including 15 human infections, have been reported in China. These repeated outbreaks have increased concern that the H5N6 virus may cross over to humans and cause a pandemic. In February, 2016, peafowls in a breeding farm exhibited a highly contagious disease. Post-mortem examinations, including RT-PCR, and virus isolation, confirmed that the highly pathogenic H5N6 influenza virus was the causative agent, and the strain was named A/Pavo Cristatus/Jiangxi/JA1/2016. In animal experiments, it exhibited high pathogenicity in chickens and an estimated median lethal dose in mice of ~104.3 TCID50. A phylogenetic analysis showed that JA1/2016 was clustered in H5 clade 2.3.4.4. FG594-like H5N6 virus from Guangdong Province was the probable predecessor of JA1/2016, and the estimated divergence time was June 2014. Furthermore, we found that H5N6 influenza viruses can be classified into the two following groups: Group 1 and Group 2. Group 2 influenza viruses have not been detected since the end of 2014, whereas Group 1 influenza viruses have continually evolved and reassorted with the “gene pool” circulating in south China, resulting in the rise of novel subtypes of this influenza virus. An increase in the number of its identified hosts, the expanding range of its distribution, and the continual evolution of H5N6 AIVs enhance the risk that an H5N6 virus may spread to other continents and cause a pandemic. PMID:28293218

Antivirals Use During the Pandemic H1N1 2009 Outbreak

Centers for Disease Control (CDC) Podcasts

2012-01-23

Charisma Atkins, CDC public health analyst, discusses antiviral use during the 2009 H1N1 pandemic flu outbreak.  Created: 1/23/2012 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 1/23/2012.

Spatial and temporal association of outbreaks of H5N1 influenza virus infection in wild birds with the 0 degrees C isotherm.

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Leslie A Reperant

2010-04-01

Full Text Available Wild bird movements and aggregations following spells of cold weather may have resulted in the spread of highly pathogenic avian influenza virus (HPAIV H5N1 in Europe during the winter of 2005-2006. Waterbirds are constrained in winter to areas where bodies of water remain unfrozen in order to feed. On the one hand, waterbirds may choose to winter as close as possible to their breeding grounds in order to conserve energy for subsequent reproduction, and may be displaced by cold fronts. On the other hand, waterbirds may choose to winter in regions where adverse weather conditions are rare, and may be slowed by cold fronts upon their journey back to the breeding grounds, which typically starts before the end of winter. Waterbirds will thus tend to aggregate along cold fronts close to the 0 degrees C isotherm during winter, creating conditions that favour HPAIV H5N1 transmission and spread. We determined that the occurrence of outbreaks of HPAIV H5N1 infection in waterbirds in Europe during the winter of 2005-2006 was associated with temperatures close to 0 degrees C. The analysis suggests a significant spatial and temporal association of outbreaks caused by HPAIV H5N1 in wild birds with maximum surface air temperatures of 0 degrees C-2 degrees C on the day of the outbreaks and the two preceding days. At locations where waterbird census data have been collected since 1990, maximum mallard counts occurred when average and maximum surface air temperatures were 0 degrees C and 3 degrees C, respectively. Overall, the abundance of mallards (Anas platyrhynchos and common pochards (Aythya ferina was highest when surface air temperatures were lower than the mean temperatures of the region investigated. The analysis implies that waterbird movements associated with cold weather, and congregation of waterbirds along the 0 degrees C isotherm likely contributed to the spread and geographical distribution of outbreaks of HPAIV H5N1 infection in wild birds in

Outbreak of H3N2 influenza at a US military base in Djibouti during the H1N1 pandemic of 2009.

Science.gov (United States)

Cosby, Michael T; Pimentel, Guillermo; Nevin, Remington L; Fouad Ahmed, Salwa; Klena, John D; Amir, Ehab; Younan, Mary; Browning, Robert; Sebeny, Peter J

2013-01-01

Influenza pandemics have significant operational impact on deployed military personnel working in areas throughout the world. The US Department of Defense global influenza-like illness (ILI) surveillance network serves an important role in establishing baseline trends and can be leveraged to respond to outbreaks of respiratory illness. We identified and characterized an operationally unique outbreak of H3N2 influenza at Camp Lemonnier, Djibouti occurring simultaneously with the H1N1 pandemic of 2009 [A(H1N1)pdm09]. Enhanced surveillance for ILI was conducted at Camp Lemonnier in response to local reports of a possible outbreak during the A(H1N1)pdm09 pandemic. Samples were collected from consenting patients presenting with ILI (utilizing a modified case definition) and who completed a case report form. Samples were cultured and analyzed using standard real-time reverse transcriptase PCR (rt-RT-PCR) methodology and sequenced genetic material was phylogenetically compared to other published strains. rt-RT-PCR and DNA sequencing revealed that 25 (78%) of the 32 clinical samples collected were seasonal H3N2 and only 2 (6%) were A(H1N1)pdm09 influenza. The highest incidence of H3N2 occurred during the month of May and 80% of these were active duty military personnel. Phylogenetic analysis revealed that sequenced H3N2 strains were genetically similar to 2009 strains from the United States of America, Australia, and South east Asia. This outbreak highlights challenges in the investigation of influenza among deployed military populations and corroborates the public health importance of maintaining surveillance systems for ILI that can be enhanced locally when needed.

In vitro assessment of attachment pattern and replication efficiency of H5N1 influenza A viruses with altered receptor specificity.

Science.gov (United States)

Chutinimitkul, Salin; van Riel, Debby; Munster, Vincent J; van den Brand, Judith M A; Rimmelzwaan, Guus F; Kuiken, Thijs; Osterhaus, Albert D M E; Fouchier, Ron A M; de Wit, Emmie

2010-07-01

The continuous circulation of the highly pathogenic avian influenza (HPAI) H5N1 virus has been a cause of great concern. The possibility of this virus acquiring specificity for the human influenza A virus receptor, alpha2,6-linked sialic acids (SA), and being able to transmit efficiently among humans is a constant threat to human health. Different studies have described amino acid substitutions in hemagglutinin (HA) of clinical HPAI H5N1 isolates or that were introduced experimentally that resulted in an increased, but not exclusive, binding of these virus strains to alpha2,6-linked SA. We introduced all previously described amino acid substitutions and combinations thereof into a single genetic background, influenza virus A/Indonesia/5/05 HA, and tested the receptor specificity of these 27 mutant viruses. The attachment pattern to ferret and human tissues of the upper and lower respiratory tract of viruses with alpha2,6-linked SA receptor preference was then determined and compared to the attachment pattern of a human influenza A virus (H3N2). At least three mutant viruses showed an attachment pattern to the human respiratory tract similar to that of the human H3N2 virus. Next, the replication efficiencies of these mutant viruses and the effects of three different neuraminidases on virus replication were determined. These data show that influenza virus A/Indonesia/5/05 potentially requires only a single amino acid substitution to acquire human receptor specificity, while at the same time remaining replication competent, thus suggesting that the pandemic threat posed by HPAI H5N1 is far from diminished.

In Vitro Assessment of Attachment Pattern and Replication Efficiency of H5N1 Influenza A Viruses with Altered Receptor Specificity▿

Science.gov (United States)

Chutinimitkul, Salin; van Riel, Debby; Munster, Vincent J.; van den Brand, Judith M. A.; Rimmelzwaan, Guus F.; Kuiken, Thijs; Osterhaus, Albert D. M. E.; Fouchier, Ron A. M.; de Wit, Emmie

2010-01-01

The continuous circulation of the highly pathogenic avian influenza (HPAI) H5N1 virus has been a cause of great concern. The possibility of this virus acquiring specificity for the human influenza A virus receptor, α2,6-linked sialic acids (SA), and being able to transmit efficiently among humans is a constant threat to human health. Different studies have described amino acid substitutions in hemagglutinin (HA) of clinical HPAI H5N1 isolates or that were introduced experimentally that resulted in an increased, but not exclusive, binding of these virus strains to α2,6-linked SA. We introduced all previously described amino acid substitutions and combinations thereof into a single genetic background, influenza virus A/Indonesia/5/05 HA, and tested the receptor specificity of these 27 mutant viruses. The attachment pattern to ferret and human tissues of the upper and lower respiratory tract of viruses with α2,6-linked SA receptor preference was then determined and compared to the attachment pattern of a human influenza A virus (H3N2). At least three mutant viruses showed an attachment pattern to the human respiratory tract similar to that of the human H3N2 virus. Next, the replication efficiencies of these mutant viruses and the effects of three different neuraminidases on virus replication were determined. These data show that influenza virus A/Indonesia/5/05 potentially requires only a single amino acid substitution to acquire human receptor specificity, while at the same time remaining replication competent, thus suggesting that the pandemic threat posed by HPAI H5N1 is far from diminished. PMID:20392847

2009 pandemic influenza A (H1N1 virus outbreak and response--Rwanda, October, 2009-May, 2010.

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Justin Wane

Full Text Available BACKGROUND: In October 2009, the first case of pandemic influenza A(H1N1pdm09 (pH1N1 was confirmed in Kigali, Rwanda and countrywide dissemination occurred within several weeks. We describe clinical and epidemiological characteristics of this epidemic. METHODS: From October 2009 through May 2010, we undertook epidemiologic investigations and response to pH1N1. Respiratory specimens were collected from all patients meeting the WHO case definition for pH1N1, which were tested using CDC's real time RT-PCR protocol at the Rwandan National Reference Laboratory (NRL. Following documented viral transmission in the community, testing focused on clinically severe and high-risk group suspect cases. RESULTS: From October 9, 2009 through May 31, 2010, NRL tested 2,045 specimens. In total, 26% (n = 532 of specimens tested influenza positive; of these 96% (n = 510 were influenza A and 4% (n = 22 were influenza B. Of cases testing influenza A positive, 96.8% (n = 494, 3% (n = 15, and 0.2% (n = 1 were A(H1N1pdm09, Seasonal A(H3 and Seasonal A(non-subtyped, respectively. Among laboratory-confirmed cases, 263 (53.2% were children <15 years and 275 (52% were female. In total, 58 (12% cases were hospitalized with mean duration of hospitalization of 5 days (Range: 2-15 days. All cases recovered and there were no deaths. Overall, 339 (68% confirmed cases received oseltamivir in any setting. Among all positive cases, 26.9% (143/532 were among groups known to be at high risk of influenza-associated complications, including age <5 years 23% (122/532, asthma 0.8% (4/532, cardiac disease 1.5% (8/532, pregnancy 0.6% (3/532, diabetes mellitus 0.4% (2/532, and chronic malnutrition 0.8% (4/532. CONCLUSIONS: Rwanda experienced a PH1N1 outbreak which was epidemiologically similar to PH1N1 outbreaks in the region. Unlike seasonal influenza, children <15 years were the most affected by pH1N1. Lessons learned from the outbreak response included the need to

Protection level of AI H5N1 vaccine clade 2.1.3 commercial against AI H5N1 clade 2.3.2 virus from Ducks to SPF chicken in laboratory conditions

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Indriani R

2015-03-01

Full Text Available Highly Pathogenic Avian Influenza (HPAI subtype H5N1 clade 2.3.2 has infected chickens in farms, causing mortality and a decrease in egg production. Vaccination is one of the strategies to control disease of AI subtype H5N1. AI H5N1 clade 2.1.3 vaccine is available commercially. The effectiveness of two vaccines of AI H5N1 clade 2.1.3 (product A and B, and AI H5N1 clade 2.3.2 (Sukoharjo against AI H5N1 clade 2.3.2 (Sukoharjo virus SPF chickens was tested in laboratory. Four groups of SPF chickens were used in this study, there were (1 vaccinated with H5N1 clade 2.1.3 (product A, (2 vaccinated with H5N1 clade 2.1.3 (product B, (3 vaccinated with AI H5N1 clade 2.3.2 and (4 unvaccinated (as a control. Each vaccinated group consisted of 10 chicken except 8 chicken for control group. SPF chicken were vaccinated with 1 dose of vaccine at 3 weeks olds, and then after 3 weeks post vaccination (at 6 weeks olds. All group of chicken were challenged with 106 EID50 per 0.1 ml via intranasal. The results showed, chicken vaccinated with H5N1 clade 2.1.3 product A and B gave 100 and 80% protection respectively, but showed challenged virus shedding, whereas vaccine of H5N1 clade 2.3.2 gave 100% protection from mortality and without virus shedding. Vaccines of AI H5N1 clade 2.1.3 product A was better than vaccine product B, and when chicken vaccinated against H5N1 clade 2.3.2, H5N1 clade 2.3.2 vaccine was the best to be used. In order to protect chicken from AI subtype H5N1 clade 2.1.3 and 2.3.2 in the field, a bivalent vaccine of H5N1 clade 2.1.3 and 2.3.2 subtypes should be developed.

Outbreak of H3N2 influenza at a US military base in Djibouti during the H1N1 pandemic of 2009.

Directory of Open Access Journals (Sweden)

Michael T Cosby

Full Text Available BACKGROUND: Influenza pandemics have significant operational impact on deployed military personnel working in areas throughout the world. The US Department of Defense global influenza-like illness (ILI surveillance network serves an important role in establishing baseline trends and can be leveraged to respond to outbreaks of respiratory illness. OBJECTIVE: We identified and characterized an operationally unique outbreak of H3N2 influenza at Camp Lemonnier, Djibouti occurring simultaneously with the H1N1 pandemic of 2009 [A(H1N1pdm09]. METHODS: Enhanced surveillance for ILI was conducted at Camp Lemonnier in response to local reports of a possible outbreak during the A(H1N1pdm09 pandemic. Samples were collected from consenting patients presenting with ILI (utilizing a modified case definition and who completed a case report form. Samples were cultured and analyzed using standard real-time reverse transcriptase PCR (rt-RT-PCR methodology and sequenced genetic material was phylogenetically compared to other published strains. RESULTS: rt-RT-PCR and DNA sequencing revealed that 25 (78% of the 32 clinical samples collected were seasonal H3N2 and only 2 (6% were A(H1N1pdm09 influenza. The highest incidence of H3N2 occurred during the month of May and 80% of these were active duty military personnel. Phylogenetic analysis revealed that sequenced H3N2 strains were genetically similar to 2009 strains from the United States of America, Australia, and South east Asia. CONCLUSIONS: This outbreak highlights challenges in the investigation of influenza among deployed military populations and corroborates the public health importance of maintaining surveillance systems for ILI that can be enhanced locally when needed.

Host-specific exposure and fatal neurologic disease in wild raptors from highly pathogenic avian influenza virus H5N1 during the 2006 outbreak in Germany.

Science.gov (United States)

van den Brand, Judith Ma; Krone, Oliver; Wolf, Peter U; van de Bildt, Marco W G; van Amerongen, Geert; Osterhaus, Albert D M E; Kuiken, Thijs

2015-03-05

Raptors may contract highly pathogenic avian influenza virus H5N1 by hunting or scavenging infected prey. However, natural H5N1 infection in raptors is rarely reported. Therefore, we tested raptors found dead during an H5N1 outbreak in wild waterbirds in Mecklenburg-Western Pomerania, Germany, in 2006 for H5N1-associated disease. We tested 624 raptors of nine species-common buzzard (385), Eurasian sparrowhawk (111), common kestrel (38), undetermined species of buzzard (36), white-tailed sea eagle (19), undetermined species of raptor (12), northern goshawk (10), peregrine falcon (6), red kite (3), rough-legged buzzard (3), and western marsh-harrier (1)-for H5N1 infection in tracheal or combined tracheal/cloacal swabs of all birds, and on major tissues of all white-tailed sea eagles. H5N1 infection was detected in two species: common buzzard (12 positive, 3.1%) and peregrine falcon (2 positive, 33.3%). In all necropsied birds (both peregrine falcons and the six freshest common buzzards), H5N1 was found most consistently and at the highest concentration in the brain, and the main H5N1-associated lesion was marked non-suppurative encephalitis. Other H5N1-associated lesions occurred in air sac, lung, oviduct, heart, pancreas, coelomic ganglion, and adrenal gland. Our results show that the main cause of death in H5N1-positive raptors was encephalitis. Our results imply that H5N1 outbreaks in wild waterbirds are more likely to lead to exposure to and mortality from H5N1 in raptors that hunt or scavenge medium-sized birds, such as common buzzards and peregrine falcons, than in raptors that hunt small birds and do not scavenge, such as Eurasian sparrowhawks and common kestrels.

Comparing introduction to Europe of highly pathogenic avian influenza viruses A(H5N8) in 2014 and A(H5N1) in 2005

NARCIS (Netherlands)

Adlhoch, C.; Gossner, C.; Koch, G.; Brown, I.; Bouwstra, R.J.; Verdonck, F.; Penttinen, P.; Harder, T.

2014-01-01

Since the beginning of November 2014, nine outbreaks of highly pathogenic avian influenza virus (HPAIV) A(H5N8) in poultry have been detected in four European countries. In this report, similarities and differences between the modes of introduction of HPAIV A(H5N1) and A(H5N8) into Europe are

Hazard analysis of critical control points assessment as a tool to respond to emerging infectious disease outbreaks.

Directory of Open Access Journals (Sweden)

Kelly L Edmunds

Full Text Available Highly pathogenic avian influenza virus (HPAI strain H5N1 has had direct and indirect economic impacts arising from direct mortality and control programmes in over 50 countries reporting poultry outbreaks. HPAI H5N1 is now reported as the most widespread and expensive zoonotic disease recorded and continues to pose a global health threat. The aim of this research was to assess the potential of utilising Hazard Analysis of Critical Control Points (HACCP assessments in providing a framework for a rapid response to emerging infectious disease outbreaks. This novel approach applies a scientific process, widely used in food production systems, to assess risks related to a specific emerging health threat within a known zoonotic disease hotspot. We conducted a HACCP assessment for HPAI viruses within Vietnam's domestic poultry trade and relate our findings to the existing literature. Our HACCP assessment identified poultry flock isolation, transportation, slaughter, preparation and consumption as critical control points for Vietnam's domestic poultry trade. Introduction of the preventative measures highlighted through this HACCP evaluation would reduce the risks posed by HPAI viruses and pressure on the national economy. We conclude that this HACCP assessment provides compelling evidence for the future potential that HACCP analyses could play in initiating a rapid response to emerging infectious diseases.

Detection and Characterization of Clade 1 Reassortant H5N1 Viruses Isolated from Human Cases in Vietnam during 2013.

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Sharmi W Thor

Full Text Available Highly pathogenic avian influenza (HPAI H5N1 is endemic in Vietnamese poultry and has caused sporadic human infection in Vietnam since 2003. Human infections with HPAI H5N1 are of concern due to a high mortality rate and the potential for the emergence of pandemic viruses with sustained human-to-human transmission. Viruses isolated from humans in southern Vietnam have been classified as clade 1 with a single genome constellation (VN3 since their earliest detection in 2003. This is consistent with detection of this clade/genotype in poultry viruses endemic to the Mekong River Delta and surrounding regions. Comparison of H5N1 viruses detected in humans from southern Vietnamese provinces during 2012 and 2013 revealed the emergence of a 2013 reassortant virus with clade 1.1.2 hemagglutinin (HA and neuraminidase (NA surface protein genes but internal genes derived from clade 2.3.2.1a viruses (A/Hubei/1/2010-like; VN12. Closer analysis revealed mutations in multiple genes of this novel genotype (referred to as VN49 previously associated with increased virulence in animal models and other markers of adaptation to mammalian hosts. Despite the changes identified between the 2012 and 2013 genotypes analyzed, their virulence in a ferret model was similar. Antigenically, the 2013 viruses were less cross-reactive with ferret antiserum produced to the clade 1 progenitor virus, A/Vietnam/1203/2004, but reacted with antiserum produced against a new clade 1.1.2 WHO candidate vaccine virus (A/Cambodia/W0526301/2012 with comparable hemagglutination inhibition titers as the homologous antigen. Together, these results indicate changes to both surface and internal protein genes of H5N1 viruses circulating in southern Vietnam compared to 2012 and earlier viruses.

Outbreak of pandemic influenza A/H1N1 2009 in Nepal.

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Adhikari, Bal Ram; Shakya, Geeta; Upadhyay, Bishnu Prasad; Prakash Kc, Khagendra; Shrestha, Sirjana Devi; Dhungana, Guna Raj

2011-03-23

The 2009 flu pandemic is a global outbreak of a new strain of H1N1 influenza virus. Pandemic influenza A (H1N1) 2009 has posed a serious public health challenge world-wide. Nepal has started Laboratory diagnosis of Pandemic influenza A/H1N1 from mid June 2009 though active screening of febrile travellers with respiratory symptoms was started from April 27, 2009. Out of 609 collected samples, 302 (49.6%) were Universal Influenza A positive. Among the influenza A positive samples, 172(28.3%) were positive for Pandemic influenza A/H1N1 and 130 (21.3%) were Seasonal influenza A. Most of the pandemic cases (53%) were found among young people with ≤ 20 years. Case Fatality Ratio for Pandemic influenza A/H1N1 in Nepal was 1.74%. Upon Molecular characterization, all the isolated pandemic influenza A/H1N1 2009 virus found in Nepal were antigenically and genetically related to the novel influenza A/CALIFORNIA/07/2009-LIKE (H1N1)v type. The Pandemic 2009 influenza virus found in Nepal were antigenically and genetically related to the novel A/CALIFORNIA/07/2009-LIKE (H1N1)v type.

Outbreak of pandemic influenza A/H1N1 2009 in Nepal

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Shrestha Sirjana

2011-03-01

Full Text Available Abstract Background The 2009 flu pandemic is a global outbreak of a new strain of H1N1 influenza virus. Pandemic influenza A (H1N1 2009 has posed a serious public health challenge world-wide. Nepal has started Laboratory diagnosis of Pandemic influenza A/H1N1 from mid June 2009 though active screening of febrile travellers with respiratory symptoms was started from April 27, 2009. Results Out of 609 collected samples, 302 (49.6% were Universal Influenza A positive. Among the influenza A positive samples, 172(28.3% were positive for Pandemic influenza A/H1N1 and 130 (21.3% were Seasonal influenza A. Most of the pandemic cases (53% were found among young people with ≤ 20 years. Case Fatality Ratio for Pandemic influenza A/H1N1 in Nepal was 1.74%. Upon Molecular characterization, all the isolated pandemic influenza A/H1N1 2009 virus found in Nepal were antigenically and genetically related to the novel influenza A/CALIFORNIA/07/2009-LIKE (H1N1v type. Conclusion The Pandemic 2009 influenza virus found in Nepal were antigenically and genetically related to the novel A/CALIFORNIA/07/2009-LIKE (H1N1v type.

Dynamic of H5N1 virus in Cambodia and emergence of a novel endemic sub-clade.

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Sorn, San; Sok, Touch; Ly, Sovann; Rith, Sareth; Tung, Nguyen; Viari, Alain; Gavotte, Laurent; Holl, Davun; Seng, Heng; Asgari, Nima; Richner, Beat; Laurent, Denis; Chea, Nora; Duong, Veasna; Toyoda, Tetsuya; Yasuda, Chadwick Y; Kitsutani, Paul; Zhou, Paul; Bing, Sun; Deubel, Vincent; Donis, Ruben; Frutos, Roger; Buchy, Philippe

2013-04-01

In Cambodia, the first detection of HPAI H5N1 virus in birds occurred in January 2004 and since then there have been 33 outbreaks in poultry while 21 human cases were reported. The origin and dynamics of these epizootics in Cambodia remain unclear. In this work we used a range of bioinformatics methods to analyze the Cambodian virus sequences together with those from neighboring countries. Six HA lineages belonging to clades 1 and 1.1 were identified since 2004. Lineage 1 shares an ancestor with viruses from Thailand and disappeared after 2005, to be replaced by lineage 2 originating from Vietnam and then by lineage 3. The highly adapted lineage 4 was seen only in Cambodia. Lineage 5 is circulating both in Vietnam and Cambodia since 2008 and was probably introduced in Cambodia through unregistered transboundary poultry trade. Lineage 6 is endemic to Cambodia since 2010 and could be classified as a new clade according to WHO/OIE/FAO criteria for H5N1 virus nomenclature. We propose to name it clade 1.1A. There is a direct filiation of lineages 2 to 6 with a temporal evolution and geographic differentiation for lineages 4 and 6. By the end of 2011, two lineages, i.e. lineages 5 and 6, with different transmission paths cocirculate in Cambodia. The presence of lineage 6 only in Cambodia suggests the existence of a transmission specific to this country whereas the presence of lineage 5 in both Cambodia and Vietnam indicates a distinct way of circulation of infected poultry. Copyright © 2012 Elsevier B.V. All rights reserved.

H5N2 Highly Pathogenic Avian Influenza Viruses from the US 2014-2015 outbreak have an unusually long pre-clinical period in turkeys.

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Spackman, Erica; Pantin-Jackwood, Mary J; Kapczynski, Darrell R; Swayne, David E; Suarez, David L

2016-11-22

From December 2014 through June 2015, the US experienced the most costly highly pathogenic avian influenza (HPAI) outbreak to date. Most cases in commercial poultry were caused by an H5N2 strain which was a reassortant with 5 Eurasian lineage genes, including a clade 2.3.4.4 goose/Guangdong/1996 lineage hemagglutinin, and 3 genes from North American wild waterfowl low pathogenicity avian influenza viruses. The outbreak primarily affected turkeys and table-egg layer type chickens. Three isolates were selected for characterization in turkeys: the US index isolate from December 2014 (A/northern pintail/WA/40964/2014), and two poultry isolates from April 2015 (A/chicken/IA/13388/2015 and A/turkey/MN/12528/2015). Four week old broad-breasted white turkeys were inoculated with one of three doses (10 2 , 10 4 or 10 6 50% egg infectious doses [EID 50 ] per bird) of each of the isolates to evaluate infectious dose and pathogenesis. The mean bird infectious dose of A/northern pintail/WA/40964/2014 and A/turkey/MN/12528/2015 was 10 5 EID 50 per bird, but was 10 3 EID 50 per bird for A/chicken/IA/13388/2015, suggesting the latter had greater adaptation to gallinaceous birds. All three isolates had unusually long mean death time of 5.3-5.9 days post challenge, and the primary clinical signs were severe lethargy and neurological signs which started no more than 24 h before death (the average pre-clinical period was 4 days). Infected turkeys also shed high levels of virus by both the oropharyngeal and cloacal routes. The unusually long mean death times, high levels of virus in feces, and increased adaptation of the later viruses may have contributed to the rapid spread of the virus during the peak of the outbreak.

The Intersection of Care Seeking and Clinical Capacity for Patients With Highly Pathogenic Avian Influenza A (H5N1) Virus in Indonesia: Knowledge and Treatment Practices of the Public and Physicians.

Science.gov (United States)

Kreslake, Jennifer M; Wahyuningrum, Yunita; Iuliano, Angela D; Storms, Aaron D; Lafond, Kathryn E; Mangiri, Amalya; Praptiningsih, Catharina Y; Safi, Basil; Uyeki, Timothy M; Storey, J Douglas

2016-12-01

Indonesia has the highest human mortality from highly pathogenic avian influenza (HPAI) A (H5N1) virus infection in the world. A survey of households (N=2520) measured treatment sources and beliefs among symptomatic household members. A survey of physicians (N=554) in various types of health care facilities measured knowledge, assessment and testing behaviors, and perceived clinical capacity. Households reported confidence in health care system capacity but infrequently sought treatment for potential HPAI H5N1 signs/symptoms. More clinicians were confident in their knowledge of diagnosis and treatment than in the adequacy of related equipment and resources at their facilities. Physicians expressed awareness of the HPAI H5N1 suspect case definition, yet expressed only moderate knowledge in questioning symptomatic patients about exposures. Self-reported likelihood of testing for HPAI H5N1 virus was high after learning of certain exposures. Knowledge of antiviral treatment was moderate, but it was higher among clinicians in puskesmas. Physicians in private outpatient clinics, the most heavily used facilities, reported the lowest confidence in their diagnostic and treatment capabilities. Educational campaigns can encourage recall of possible poultry exposure when patients are experiencing signs/symptoms and can raise awareness of the effectiveness of antivirals to drive people to seek health care. Clinicians may benefit from training regarding exposure assessment and referral procedures, particularly in private clinics. (Disaster Med Public Health Preparedness. 2016;10:838-847).

Virulence of H5N1 Influenza Virus in Cattle Egrets (Bubulcus Ibis)

DEFF Research Database (Denmark)

Phuong, Do Quy; Dung, Nguyen Tien; Jørgensen, Poul Henrik

2011-01-01

for insect control in households. In this study, six Cattle Egrets were experimentally infected intranasally with highly pathogenic avian influenza (AI) A/duck/Vietnam/40D/04 (H5N1) to investigate a possible epidemiologic role for Cattle Egrets in outbreaks of H5N1 AI in Vietnam. The Cattle Egrets were...

Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highly pathogenic influenza intranasal and intratracheal challenge.

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Alex J Mann

Full Text Available We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments or intranasally (CSN adjuvanted and placebo treatments only with clade 1 HPAI A/Vietnam/1194/2004 (H5N1 virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings. In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratracheal challenge; serologically, protective titres were demonstrable after one vaccination. The 2-dose schedule with TM-CSN vaccine also induced cross-reactive antibodies to clade 2.1 and 2.2 H5N1 viruses. Furthermore ferrets immunised with TM-CSN had no detectable virus in the respiratory tract or brain, whereas there were signs of virus in the throat and lungs, albeit at significantly reduced levels, in CSN vaccinated animals. This study demonstrated for the first time that CSN and in particular TM-CSN adjuvanted intranasal vaccines have the potential to protect against significant

Retrospective space-time analysis of H5N1 Avian Influenza emergence in Thailand

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Shanmugasundaram Jothiganesh

2010-01-01

Full Text Available Abstract Background The highly pathogenic avian influenza (HPAI H5N1 virus remains a worldwide threat to human and animal health, while the mechanisms explaining its epizootic emergence and re-emergence in poultry are largely unknown. Data from Thailand, a country that experienced significant epidemics in poultry and has recorded suspicious cases of HPAI on a daily basis since 2004, are used here to study the process of emergence. A spatial approach is employed to describe all HPAI H5N1 virus epizootics from 2004 to 2008 and to characterize the pattern of emergence: multiple independent introductions of the virus followed by moderate local spread vs. very rare emergences followed by strong local spread and rare long range diffusion jumps. Sites where epizootics originate (by foreign introduction, local persistence, or long range jump were selected from those to which the disease subsequently spreads using a filter based on relative date and position. The spatial distribution of these selected foci was statistically analyzed, and to differentiate environmental factors from long range diffusion, we investigate the relationship of these foci with environmental exposure factors and with rearing characteristics. Results During each wave of epizootics, the temporal occurrence of cases did not show a temporal interruption of more than a week. All foci were globally clustered; i.e., more than 90% of cases had a previous case within a 10 km range and a 21 day period of time, showing a strong local spread. We were able to estimate 60 km as the maximum distance for the local farm to farm dissemination process. The remaining "emergent" cases have occurred randomly over Thailand and did not show specific location, clusters, or trends. We found that these foci are not statistically related to specific environmental conditions or land cover characteristics, and most of them may be interpreted as long range diffusion jumps due to commercial practices

Virus-like particles displaying H5, H7, H9 hemagglutinins and N1 neuraminidase elicit protective immunity to heterologous avian influenza viruses in chickens

International Nuclear Information System (INIS)

Pushko, Peter; Tretyakova, Irina; Hidajat, Rachmat; Zsak, Aniko; Chrzastek, Klaudia; Tumpey, Terrence M.; Kapczynski, Darrell R.

2017-01-01

Avian influenza (AI) viruses circulating in wild birds pose a serious threat to public health. Human and veterinary vaccines against AI subtypes are needed. Here we prepared triple-subtype VLPs that co-localized H5, H7 and H9 antigens derived from H5N1, H7N3 and H9N2 viruses. VLPs also contained influenza N1 neuraminidase and retroviral gag protein. The H5/H7/H9/N1/gag VLPs were prepared using baculovirus expression. Biochemical, functional and antigenic characteristics were determined including hemagglutination and neuraminidase enzyme activities. VLPs were further evaluated in a chicken AI challenge model for safety, immunogenicity and protective efficacy against heterologous AI viruses including H5N2, H7N3 and H9N2 subtypes. All vaccinated birds survived challenges with H5N2 and H7N3 highly pathogenic AI (HPAI) viruses, while all controls died. Immune response was also detectable after challenge with low pathogenicity AI (LPAI) H9N2 virus suggesting that H5/H7/H9/N1/gag VLPs represent a promising approach for the development of broadly protective AI vaccine. - Highlights: •VLPs were prepared that co-localized H5, H7 and H9 subtypes in a VLP envelope. •VLPs were characterized including electron microscopy, HA assay and NA enzyme activity. •Experimental VLP vaccine was evaluated in an avian influenza challenge model. •VLPs induced immune responses against heterologous H5, H7 and H9 virus challenges.

Virus-like particles displaying H5, H7, H9 hemagglutinins and N1 neuraminidase elicit protective immunity to heterologous avian influenza viruses in chickens

Energy Technology Data Exchange (ETDEWEB)

Pushko, Peter, E-mail: ppushko@medigen-usa.com [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701 (United States); Tretyakova, Irina; Hidajat, Rachmat [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701 (United States); Zsak, Aniko; Chrzastek, Klaudia [USDA SEPRL, 934 College Station Rd, Athens, GA (United States); Tumpey, Terrence M. [Influenza Division, CDC,1600 Clifton Road N.E., Atlanta, GA (United States); Kapczynski, Darrell R. [USDA SEPRL, 934 College Station Rd, Athens, GA (United States)

2017-01-15

Avian influenza (AI) viruses circulating in wild birds pose a serious threat to public health. Human and veterinary vaccines against AI subtypes are needed. Here we prepared triple-subtype VLPs that co-localized H5, H7 and H9 antigens derived from H5N1, H7N3 and H9N2 viruses. VLPs also contained influenza N1 neuraminidase and retroviral gag protein. The H5/H7/H9/N1/gag VLPs were prepared using baculovirus expression. Biochemical, functional and antigenic characteristics were determined including hemagglutination and neuraminidase enzyme activities. VLPs were further evaluated in a chicken AI challenge model for safety, immunogenicity and protective efficacy against heterologous AI viruses including H5N2, H7N3 and H9N2 subtypes. All vaccinated birds survived challenges with H5N2 and H7N3 highly pathogenic AI (HPAI) viruses, while all controls died. Immune response was also detectable after challenge with low pathogenicity AI (LPAI) H9N2 virus suggesting that H5/H7/H9/N1/gag VLPs represent a promising approach for the development of broadly protective AI vaccine. - Highlights: •VLPs were prepared that co-localized H5, H7 and H9 subtypes in a VLP envelope. •VLPs were characterized including electron microscopy, HA assay and NA enzyme activity. •Experimental VLP vaccine was evaluated in an avian influenza challenge model. •VLPs induced immune responses against heterologous H5, H7 and H9 virus challenges.

Highly Pathogenic Avian Influenza H5N8 Clade 2.3.4.4 Virus: Equivocal Pathogenicity and Implications for Surveillance Following Natural Infection in Breeder Ducks in the United Kingdom.

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Núñez, A; Brookes, S M; Reid, S M; Garcia-Rueda, C; Hicks, D J; Seekings, J M; Spencer, Y I; Brown, I H

2016-02-01

Since early 2014, several outbreaks involving novel reassortant highly pathogenic avian influenza (HPAI) A(H5N8) viruses have been detected in poultry and wild bird species in Asia, Europe and North America. These viruses have been detected in apparently healthy and dead wild migratory birds, as well as in domestic chickens, turkeys, geese and ducks. In this study, we describe the pathology of an outbreak of H5N8 HPAIV in breeder ducks in the UK. A holding with approximately 6000 breeder ducks, aged approximately 60 weeks, showed a gradual reduction in egg production and increased mortality over a 7-day period. Post-mortem examination revealed frequent fibrinous peritonitis, with severely haemorrhagic ovarian follicles and occasional splenic and pancreatic necrosis and high incidence of mycotic granulomas in the air sacs and lung. Low-to-moderate levels of HPAI H5N8 virus were detected mainly in respiratory and digestive tract, with minor involvement of other organs. Although histopathological examination confirmed the gross pathology findings, intralesional viral antigen detection by immunohistochemistry was not observed. Immunolabelled cells were rarely only present in inflamed air sacs and serosa, usually superficial to granulomatous inflammation. Abundant bacterial microcolonies were observed in haemorrhagic ovaries and oviduct. The limited viral tissue distribution and presence of inter-current fungal and bacterial infections suggest a minor role for HPAIV H5N8 in clinical disease in layer ducks. © 2015 Crown copyright.

Spatiotemporal Structure of Molecular Evolution of H5N1 Highly Pathogenic Avian Influenza Viruses in Vietnam

OpenAIRE

Carrel, Margaret A.; Emch, Michael; Jobe, R. Todd; Moody, Aaron; Wan, Xiu-Feng

2010-01-01

Background Vietnam is one of the countries most affected by outbreaks of H5N1 highly pathogenic avian influenza viruses. First identified in Vietnam in poultry in 2001 and in humans in 2004, the virus has since caused 111 cases and 56 deaths in humans. In 2003/2004 H5N1 outbreaks, nearly the entire poultry population of Vietnam was culled. Our earlier study (Wan et al., 2008, PLoS ONE, 3(10): e3462) demonstrated that there have been at least six independent H5N1 introductions into Vietnam and...

A unique influenza A (H5N1 virus causing a focal poultry outbreak in 2007 in Manipur, India

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Raut Satish

2009-02-01

Full Text Available Abstract Background A focal H5N1 outbreak in poultry was reported from Manipur, a north-eastern state, of India, in 2007. The aim of this study was to genetically characterize the Manipur isolate to understand the relationship with other H5N1 isolates and to trace the possible source of introduction of the virus into the country. Results Characterization of the complete genome revealed that the virus belonged to clade 2.2. It was distinctly different from viruses of the three EMA sublineages of clade 2.2 but related to isolates from wild migratory waterfowl from Russia, China and Mongolia. The HA gene, had the cleavage site GERRRRKR, earlier reported in whooper swan isolates from Mongolia in 2005. A stop codon at position 29 in the PB1-F2 protein could have implications on the replication efficiency. The acquisition of polymorphisms as seen in recent isolates of 2005–07 from distinct geographical regions suggests the possibility of transportation of H5N1 viruses through migratory birds. Conclusion Considering that all eight genes of the earlier Indian isolates belonged to the EMA3 sublineage and similar strains have not been reported from neighbouring countries of the subcontinent, it appears that the virus may have been introduced independently.

Predicting Avian Influenza Co-Infection with H5N1 and H9N2 in Northern Egypt

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Sean G. Young

2016-09-01

Full Text Available Human outbreaks with avian influenza have been, so far, constrained by poor viral adaptation to non-avian hosts. This could be overcome via co-infection, whereby two strains share genetic material, allowing new hybrid strains to emerge. Identifying areas where co-infection is most likely can help target spaces for increased surveillance. Ecological niche modeling using remotely-sensed data can be used for this purpose. H5N1 and H9N2 influenza subtypes are endemic in Egyptian poultry. From 2006 to 2015, over 20,000 poultry and wild birds were tested at farms and live bird markets. Using ecological niche modeling we identified environmental, behavioral, and population characteristics of H5N1 and H9N2 niches within Egypt. Niches differed markedly by subtype. The subtype niches were combined to model co-infection potential with known occurrences used for validation. The distance to live bird markets was a strong predictor of co-infection. Using only single-subtype influenza outbreaks and publicly available ecological data, we identified areas of co-infection potential with high accuracy (area under the receiver operating characteristic (ROC curve (AUC 0.991.

Information Needs and Seeking Behavior During the H1N1 Virus Outbreak

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Majid, Shaheen

2013-03-01

Full Text Available Timely access to quality healthcare information during an outbreak plays an important role in curtailing its spread. The aim of this study was to investigate the information needs and seeking behavior of the general public in Singapore during the H1N1 pandemic. A pre-tested questionnaire was used for data collection. The convenience snowball sampling method was used and 260 working adults and tertiary-level students participated in this study. The most crucial information needs of a majority of the participants were: symptoms of H1N1, causes of the infection, preventive measures, and possible treatments. Data analysis also revealed that mass media such as television, newspapers, and radio were most frequently used for seeking the needed information. The use of human information sources was also quite high while only a small number of the respondents accessed online news and healthcare websites. About three-quarters of the participants indicated that the gathered information helped them to stay vigilant and take necessary precautionary measures. A major problem identified by the participants in using H1N1 information was the lack of understanding of certain terms used in public communications. This paper suggests certain measures for strengthening health information communication during future outbreaks.

Prophylactic and therapeutic efficacy of avian antibodies against influenza virus H5N1 and H1N1 in mice.

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Huan H Nguyen

Full Text Available BACKGROUND: Pandemic influenza poses a serious threat to global health and the world economy. While vaccines are currently under development, passive immunization could offer an alternative strategy to prevent and treat influenza virus infection. Attempts to develop monoclonal antibodies (mAbs have been made. However, passive immunization based on mAbs may require a cocktail of mAbs with broader specificity in order to provide full protection since mAbs are generally specific for single epitopes. Chicken immunoglobulins (IgY found in egg yolk have been used mainly for treatment of infectious diseases of the gastrointestinal tract. Because the recent epidemic of highly pathogenic avian influenza virus (HPAIV strain H5N1 has resulted in serious economic losses to the poultry industry, many countries including Vietnam have introduced mass vaccination of poultry with H5N1 virus vaccines. We reasoned that IgY from consumable eggs available in supermarkets in Vietnam could provide protection against infections with HPAIV H5N1. METHODS AND FINDINGS: We found that H5N1-specific IgY that are prepared from eggs available in supermarkets in Vietnam by a rapid and simple water dilution method cross-protect against infections with HPAIV H5N1 and related H5N2 strains in mice. When administered intranasally before or after lethal infection, the IgY prevent the infection or significantly reduce viral replication resulting in complete recovery from the disease, respectively. We further generated H1N1 virus-specific IgY by immunization of hens with inactivated H1N1 A/PR/8/34 as a model virus for the current pandemic H1N1/09 and found that such H1N1-specific IgY protect mice from lethal influenza virus infection. CONCLUSIONS: The findings suggest that readily available H5N1-specific IgY offer an enormous source of valuable biological material to combat a potential H5N1 pandemic. In addition, our study provides a proof-of-concept for the approach using virus

Influenza A H5N1 immigration is filtered out at some international borders.

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Robert G Wallace

2008-02-01

Full Text Available Geographic spread of highly pathogenic influenza A H5N1, the bird flu strain, appears a necessary condition for accelerating the evolution of a related human-to-human infection. As H5N1 spreads the virus diversifies in response to the variety of socioecological environments encountered, increasing the chance a human infection emerges. Genetic phylogenies have for the most part provided only qualitative evidence that localities differ in H5N1 diversity. For the first time H5N1 variation is quantified across geographic space.We constructed a statistical phylogeography of 481 H5N1 hemagglutinin genetic sequences from samples collected across 28 Eurasian and African localities through 2006. The MigraPhyla protocol showed southern China was a source of multiple H5N1 strains. Nested clade analysis indicated H5N1 was widely dispersed across southern China by both limited dispersal and long distance colonization. The UniFrac metric, a measure of shared phylogenetic history, grouped H5N1 from Indonesia, Japan, Thailand and Vietnam with those from southeastern Chinese provinces engaged in intensive international trade. Finally, H5N1's accumulative phylogenetic diversity was greatest in southern China and declined beyond. The gradient was interrupted by areas of greater and lesser phylogenetic dispersion, indicating H5N1 migration was restricted at some geopolitical borders. Thailand and Vietnam, just south of China, showed significant phylogenetic clustering, suggesting newly invasive H5N1 strains have been repeatedly filtered out at their northern borders even as both countries suffered recurring outbreaks of endemic strains. In contrast, Japan, while successful in controlling outbreaks, has been subjected to multiple introductions of the virus.The analysis demonstrates phylogenies can provide local health officials with more than hypotheses about relatedness. Pathogen dispersal, the functional relationships among disease ecologies across localities, and

In vitro assessment of attachment pattern and replication efficiency of H5N1 influenza A viruses with altered receptor specificity

NARCIS (Netherlands)

S. Chutinimitkul (Salin); D.A.J. van Riel (Debby); V.J. Munster (Vincent); J.M.A. van den Brand (Judith); G.F. Rimmelzwaan (Guus); T. Kuiken (Thijs); A.D.M.E. Osterhaus (Albert); R.A.M. Fouchier (Ron); E. de Wit (Emmie)

2010-01-01

textabstractThe continuous circulation of the highly pathogenic avian influenza (HPAI) H5N1 virus has been a cause of great concern. The possibility of this virus acquiring specificity for the human influenza A virus receptor, α2,6-linked sialic acids (SA), and being able to transmit efficiently

Challenge for One Health: Co-Circulation of Zoonotic H5N1 and H9N2 Avian Influenza Viruses in Egypt.

Science.gov (United States)

Kim, Shin-Hee

2018-03-09

Highly pathogenic avian influenza (HPAI) H5N1 viruses are currently endemic in poultry in Egypt. Eradication of the viruses has been unsuccessful due to improper application of vaccine-based control strategies among other preventive measures. The viruses have evolved rapidly with increased bird-to-human transmission efficacy, thus affecting both animal and public health. Subsequent spread of potentially zoonotic low pathogenic avian influenza (LPAI) H9N2 in poultry has also hindered efficient control of avian influenza. The H5N1 viruses acquired enhanced bird-to-human transmissibility by (1) altering amino acids in hemagglutinin (HA) that enable binding affinity to human-type receptors, (2) loss of the glycosylation site and 130 loop in the HA protein and (3) mutation of E627K in the PB2 protein to enhance viral replication in mammalian hosts. The receptor binding site of HA of Egyptian H9N2 viruses has been shown to contain the Q234L substitution along with a H191 mutation, which can increase human-like receptor specificity. Therefore, co-circulation of H5N1 and H9N2 viruses in poultry farming and live bird markets has increased the risk of human exposure, resulting in complication of the epidemiological situation and raising a concern for potential emergence of a new influenza A virus pandemic. For efficient control of infection and transmission, the efficacy of vaccine and vaccination needs to be improved with a comprehensive control strategy, including enhanced biosecurity, education, surveillance, rapid diagnosis and culling of infected poultry.

Challenge for One Health: Co-Circulation of Zoonotic H5N1 and H9N2 Avian Influenza Viruses in Egypt

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Shin-Hee Kim

2018-03-01

Full Text Available Highly pathogenic avian influenza (HPAI H5N1 viruses are currently endemic in poultry in Egypt. Eradication of the viruses has been unsuccessful due to improper application of vaccine-based control strategies among other preventive measures. The viruses have evolved rapidly with increased bird-to-human transmission efficacy, thus affecting both animal and public health. Subsequent spread of potentially zoonotic low pathogenic avian influenza (LPAI H9N2 in poultry has also hindered efficient control of avian influenza. The H5N1 viruses acquired enhanced bird-to-human transmissibility by (1 altering amino acids in hemagglutinin (HA that enable binding affinity to human-type receptors, (2 loss of the glycosylation site and 130 loop in the HA protein and (3 mutation of E627K in the PB2 protein to enhance viral replication in mammalian hosts. The receptor binding site of HA of Egyptian H9N2 viruses has been shown to contain the Q234L substitution along with a H191 mutation, which can increase human-like receptor specificity. Therefore, co-circulation of H5N1 and H9N2 viruses in poultry farming and live bird markets has increased the risk of human exposure, resulting in complication of the epidemiological situation and raising a concern for potential emergence of a new influenza A virus pandemic. For efficient control of infection and transmission, the efficacy of vaccine and vaccination needs to be improved with a comprehensive control strategy, including enhanced biosecurity, education, surveillance, rapid diagnosis and culling of infected poultry.

Avian influenza A H5N1 infections in Bali Province, Indonesia: a behavioral, virological and seroepidemiological study.

Science.gov (United States)

Santhia, Ketut; Ramy, Ayu; Jayaningsih, Putri; Samaan, Gina; Putra, Anak Agung Gde; Dibia, Nyoman; Sulaimin, Cynthia; Joni, Gusti; Leung, Connie Y H; Sriyal, Joseph; Peiris, Malik; Wandra, Toni; Kandun, Nyoman

2009-05-01

Bali Province was affected by avian influenza H5N1 outbreaks in birds in October 2003. Despite ongoing circulation of the virus, no human infection had been identified by December 2005. To assess behavioral patterns associated with poultry rearing in Bali, and to identify potential risk factors for H5N1 infection in humans and in household chickens, ducks and pigs. A behavioral, virological and seroepidemiologic survey in 38 villages and three live bird markets was completed in December 2005. A multi-stage cluster design was used to select 291 households with 841 participants from all nine districts in Bali. Specimens were collected from participants as well as a maximum of three pigs, chickens and ducks from each household. Eighty-seven market vendors participated, where specimens were collected from participants as well as chickens and ducks. Twenty out of the 38 villages sampled had H5N1 outbreaks. Despite exposure to H5N1 outbreaks, none of the participants from villages or markets were seropositive for H5N1. None of the pigs tested were positive for H5N1. Virus isolation rate in ducks and chicken in markets was higher than in households. Transport of poultry in or out of villages was a risk factor for outbreaks in household chickens and ducks. The study highlighted that the market chain and associated behaviors may play a role in maintaining the virus in household flocks. The study adds evidence that transmission of H5N1 to humans remains a rare event despite high level handling of both healthy and sick birds.

Inpatient capacity at children's hospitals during pandemic (H1N1) 2009 outbreak, United States.

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Sills, Marion R; Hall, Matthew; Fieldston, Evan S; Hain, Paul D; Simon, Harold K; Brogan, Thomas V; Fagbuyi, Daniel B; Mundorff, Michael B; Shah, Samir S

2011-09-01

Quantifying how close hospitals came to exhausting capacity during the outbreak of pandemic influenza A (H1N1) 2009 can help the health care system plan for more virulent pandemics. This ecologic analysis used emergency department (ED) and inpatient data from 34 US children's hospitals. For the 11-week pandemic (H1N1) 2009 period during fall 2009, inpatient occupancy reached 95%, which was lower than the 101% occupancy during the 2008-09 seasonal influenza period. Fewer than 1 additional admission per 10 inpatient beds would have caused hospitals to reach 100% occupancy. Using parameters based on historical precedent, we built 5 models projecting inpatient occupancy, varying the ED visit numbers and admission rate for influenza-related ED visits. The 5 scenarios projected median occupancy as high as 132% of capacity. The pandemic did not exhaust inpatient bed capacity, but a more virulent pandemic has the potential to push children's hospitals past their maximum inpatient capacity.

The Landscape Epidemiology of Seasonal Clustering of Highly Pathogenic Avian Influenza (H5N1) in Domestic Poultry in Africa, Europe and Asia.

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Walsh, M G; Amstislavski, P; Greene, A; Haseeb, M A

2017-10-01

Highly pathogenic avian influenza subtype H5N1 (H5N1) has contributed to substantial economic loss for backyard and large-scale poultry farmers each year since 1997. While the distribution of domestic H5N1 outbreaks across Africa, Europe and Asia is extensive, those features of the landscape conferring greatest risk remain uncertain. Furthermore, the extent to which influential landscape features may vary by season has been inadequately described. The current investigation used World Organization for Animal Health surveillance data to (i) delineate areas at greatest risk of H5N1 epizootics among domestic poultry, (ii) identify those abiotic and biotic features of the landscape associated with outbreak risk and (iii) examine patterns of epizootic clustering by season. Inhomogeneous point process models were used to predict the intensity of H5N1 outbreaks and describe the spatial dependencies between them. During October through March, decreasing precipitation, increasing isothermality and the presence of H5N1 in wild birds were significantly associated with the increased risk of domestic H5N1 epizootics. Conversely, increasing precipitation and decreasing isothermality were associated with the increased risk during April through September. Increasing temperature during the coldest quarter, domestic poultry density and proximity to surface water were associated with the increased risk of domestic outbreaks throughout the year. Spatial dependencies between outbreaks appeared to vary seasonally, with substantial clustering at small and large scales identified during October through March even after accounting for inhomogeneity due to landscape factors. In contrast, during April to September, H5N1 outbreaks exhibited no clustering at small scale once accounting for landscape factors. This investigation has identified seasonal differences in risk and clustering patterns of H5N1 outbreaks in domestic poultry and may suggest strategies in high-risk areas with features

Highly Pathogenic Avian Influenza A(H5N1) Virus Struck Migratory Birds in China in 2015.

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Bi, Yuhai; Zhang, Zhenjie; Liu, Wenjun; Yin, Yanbo; Hong, Jianmin; Li, Xiangdong; Wang, Haiming; Wong, Gary; Chen, Jianjun; Li, Yunfeng; Ru, Wendong; Gao, Ruyi; Liu, Di; Liu, Yingxia; Zhou, Boping; Gao, George F; Shi, Weifeng; Lei, Fumin

2015-08-11

Approximately 100 migratory birds, including whooper swans and pochards, were found dead in the Sanmenxia Reservoir Area of China during January 2015. The causative agent behind this outbreak was identified as H5N1 highly pathogenic avian influenza virus (HPAIV). Genetic and phylogenetic analyses revealed that this Sanmenxia H5N1 virus was a novel reassortant, possessing a Clade 2.3.2.1c HA gene and a H9N2-derived PB2 gene. Sanmenxia Clade 2.3.2.1c-like H5N1 viruses possess the closest genetic identity to A/Alberta/01/2014 (H5N1), which recently caused a fatal respiratory infection in Canada with signs of meningoencephalitis, a highly unusual symptom with influenza infections in humans. Furthermore, this virus was shown to be highly pathogenic to both birds and mammals, and demonstrate tropism for the nervous system. Due to the geographical location of Sanmenxia, these novel H5N1 viruses also have the potential to be imported to other regions through the migration of wild birds, similar to the H5N1 outbreak amongst migratory birds in Qinghai Lake during 2005. Therefore, further investigation and monitoring is required to prevent this novel reassortant virus from becoming a new threat to public health.

Early Outbreak of 2009 Influenza A (H1N1) in Mexico Prior to Identification of pH1N1 Virus

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Hsieh, Ying-Hen; Ma, Stefan; Velasco Hernandez, Jorge X.; Lee, Vernon J.; Lim, Wei Yen

2011-01-01

Background In the aftermath of the global spread of 2009 influenza A (pH1N1) virus, still very little is known of the early stages of the outbreak in Mexico during the early months of the year, before the virus was identified. Methodology/Main Findings We fit a simple mathematical model, the Richards model, to the number of excess laboratory-confirmed influenza cases in Mexico and Mexico City during the first 15 weeks in 2009 over the average influenza case number of the previous five baseline years of 2004-2008 during the same period to ascertain the turning point (or the peak incidence) of a wave of early influenza infections, and to estimate the transmissibility of the virus during these early months in terms of its basic reproduction number. The results indicate that there may have been an early epidemic in Mexico City as well as in all of Mexico during February/March. Based on excess influenza cases, the estimated basic reproduction number R0 for the early outbreak was 1.59 (0.55 to 2.62) for Mexico City during weeks 5–9, and 1.25 (0.76, 1.74) for all of Mexico during weeks 5–14. Conclusions We established the existence of an early epidemic in Mexico City and in all of Mexico during February/March utilizing the routine influenza surveillance data, although the location of seeding is unknown. Moreover, estimates of R0 as well as the time of peak incidence (the turning point) for Mexico City and all of Mexico indicate that the early epidemic in Mexico City in February/March had been more transmissible (larger R0) and peaked earlier than the rest of the country. Our conclusion lends support to the possibility that the virus could have already spread to other continents prior to the identification of the virus and the reporting of lab-confirmed pH1N1 cases in North America in April. PMID:21909366

Control of H1N1 influenza outbreak: A study conducted in a naval warship

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Arun Gupta

2017-01-01

Full Text Available Introduction: In confined afloat settings, the threat of an acceleration of the Influenza outbreak is substantial, causing high morbidity of the personnel on board, disrupting daily activities, and leading to low crew morale. In this study, H1N1 Influenza outbreak in a Naval Warship and its control measures are described. Materials and Methods: It is a study of 21 clinically suspected cases of H1N1 Influenza. Cases were reported within 3 weeks from a ship company, all of whom were susceptible. They have been described on the basis of demography, clinical features, recent travel history, and history of contact. Results: Mean age of the clinically suspected cases was 26.71 years. Of 21 suspected cases, 14 were found positive for the disease. Nine cases were admitted to the hospital and two developed complications. Attack rate of the disease was 4.83%. Conclusion: In confined afloat settings, prompt public health measures of active case finding, strict isolation, and adherence to hand hygiene, following cough etiquettes and disinfection enhancement, can effectively mitigate the outbreak. Vaccination may not have a role to play if preventive measures are instituted effectively.

Identifying risk factors of highly pathogenic avian influenza (H5N1 subtype) in Indonesia.

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Loth, Leo; Gilbert, Marius; Wu, Jianmei; Czarnecki, Christina; Hidayat, Muhammad; Xiao, Xiangming

2011-10-01

Highly pathogenic avian influenza (HPAI), subtype H5N1, was first officially reported in Indonesia in 2004. Since then the disease has spread and is now endemic in large parts of the country. This study investigated the statistical relationship between a set of risk factors and the presence or absence of HPAI in Indonesia during 2006 and 2007. HPAI was evaluated through participatory disease surveillance (PDS) in backyard village chickens (the study population), and risk factors included descriptors of people and poultry distribution (separating chickens, ducks and production sectors), poultry movement patterns and agro-ecological conditions. The study showed that the risk factors "elevation", "human population density" and "rice cropping" were significant in accounting for the spatial variation of the PDS-defined HPAI cases. These findings were consistent with earlier studies in Thailand and Vietnam. In addition "commercial poultry population", and two indicators of market locations and transport; "human settlements" and "road length", were identified as significant risk factors in the models. In contrast to several previous studies carried out in Southeast Asia, domestic backyard ducks were not found to be a significant risk factor in Indonesia. The study used surrogate estimates of market locations and marketing chains and further work should focus on the actual location of the live bird markets, and on the flow of live poultry and poultry products between them, so that patterns of possible transmission, and regions of particular risk could be better inferred. Copyright © 2011 Elsevier B.V. All rights reserved.

Avian influenza H5N1 transmission in households, Indonesia.

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Tjandra Y Aditama

Full Text Available BACKGROUND: Disease transmission patterns are needed to inform public health interventions, but remain largely unknown for avian influenza H5N1 virus infections. A recent study on the 139 outbreaks detected in Indonesia between 2005 and 2009 found that the type of exposure to sources of H5N1 virus for both the index case and their household members impacted the risk of additional cases in the household. This study describes the disease transmission patterns in those outbreak households. METHODOLOGY/PRINCIPAL FINDINGS: We compared cases (n = 177 and contacts (n = 496 in the 113 sporadic and 26 cluster outbreaks detected between July 2005 and July 2009 to estimate attack rates and disease intervals. We used final size household models to fit transmission parameters to data on household size, cases and blood-related household contacts to assess the relative contribution of zoonotic and human-to-human transmission of the virus, as well as the reproduction number for human virus transmission. The overall household attack rate was 18.3% and secondary attack rate was 5.5%. Secondary attack rate remained stable as household size increased. The mean interval between onset of subsequent cases in outbreaks was 5.6 days. The transmission model found that human transmission was very rare, with a reproduction number between 0.1 and 0.25, and the upper confidence bounds below 0.4. Transmission model fit was best when the denominator population was restricted to blood-related household contacts of index cases. CONCLUSIONS/SIGNIFICANCE: The study only found strong support for human transmission of the virus when a single large cluster was included in the transmission model. The reproduction number was well below the threshold for sustained transmission. This study provides baseline information on the transmission dynamics for the current zoonotic virus and can be used to detect and define signatures of a virus with increasing capacity for human

Newcastle disease virus-based H5 influenza vaccine protects chickens from lethal challenge with a highly pathogenic H5N2 avian influenza virus

OpenAIRE

Ma, Jingjiao; Lee, Jinhwa; Liu, Haixia; Mena, Ignacio; Davis, A. Sally; Sunwoo, Sun Young; Lang, Yuekun; Duff, Michael; Morozov, Igor; Li, Yuhao; Yang, Jianmei; García-Sastre, Adolfo; Richt, Juergen A.; Ma, Wenjun

2017-01-01

Since December 2014, Eurasian-origin, highly pathogenic avian influenza H5 viruses including H5N1, H5N2, and H5N8 subtypes (called H5Nx viruses), which belong to the H5 clade 2.3.4.4, have been detected in U.S. wild birds. Subsequently, highly pathogenic H5N2 and H5N8 viruses have caused outbreaks in U.S. domestic poultry. Vaccination is one of the most effective ways to control influenza outbreaks and protect animal and public health. Newcastle disease virus (NDV)-based influenza vaccines ha...

An Outbreak of 2009 Pandemic Influenza A (H1N1) Virus Infection in an Elementary School in Pennsylvania

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Bhattarai, Achuyt; Fagan, Ryan P.; Ostroff, Stephen; Sodha, Samir V.; Moll, Mària E.; Lee, Bruce Y.; Chang, Chung-Chou H.; Ennis, Brent; Britz, Phyllis; Fiore, Anthony; Nguyen, Michael; Palekar, Rakhee; Archer, W. Roodly; Gift, Thomas L.; Leap, Rebecca; Nygren, Benjamin L.; Cauchemez, Simon; Angulo, Frederick J.; Swerdlow, David

2011-01-01

In May 2009, one of the earliest outbreaks of 2009 pandemic influenza A virus (pH1N1) infection resulted in the closure of a semi-rural Pennsylvania elementary school. Two sequential telephone surveys were administered to 1345 students (85% of the students enrolled in the school) and household members in 313 households to collect data on influenza-like illness (ILI). A total of 167 persons (12.4%) among those in the surveyed households, including 93 (24.0%) of the School A students, reported ILI. Students were 3.1 times more likely than were other household members to develop ILI (95% confidence interval [CI], 2.3–4.1). Fourth-grade students were more likely to be affected than were students in other grades (relative risk, 2.2; 95% CI, 1.2–3.9). pH1N1 was confirmed in 26 (72.2%) of the individuals tested by real-time reverse-transcriptase polymerase chain reaction. The outbreak did not resume upon the reopening of the school after the 7-day closure. This investigation found that pH1N1 outbreaks at schools can have substantial attack rates; however, grades and classrooms are affected variably. Additioanl study is warranted to determine the effectiveness of school closure during outbreaks. PMID:21342888

Influence of Novel Highly Pathogenic Avian Influenza A (H5N1 Virus Infection on Migrating Whooper Swans Fecal Microbiota

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Na Zhao

2018-02-01

Full Text Available The migration of wild birds plays an important role in the transmission and spread of H5 highly pathogenic avian influenza (HPAI virus, posing a severe risk to animal and human health. Substantial evidence suggests that altered gut microbial community is implicated in the infection of respiratory influenza virus. However, the influence of H5N1 infection in gut microbiota of migratory birds remains unknown. In January 2015, a novel recombinant H5N1 virus emerged and killed about 100 migratory birds, mainly including whooper swans in Sanmenxia Reservoir Area of China. Here, we describe the first fecal microbiome diversity study of H5N1-infected migratory birds. By investigating the influence of H5N1 infection on fecal bacterial communities in infected and uninfected individuals, we found that H5N1 infection shaped the gut microbiota composition by a difference in the dominance of some genera, such as Aeromonas and Lactobacillus. We also found a decreased α diversity and increased β diversity in infectious individuals. Our results highlight that increases in changes in pathogen-containing gut communities occur when individuals become infected with H5N1. Our study may provide the first evidence that there are statistical association among H5N1 presence and fecal microbiota compositional shifts, and properties of the fecal microbiota may serve as the risk of gut-linked disease in migrates with H5N1 and further aggravate the disease transmission.

Influence of Novel Highly Pathogenic Avian Influenza A (H5N1) Virus Infection on Migrating Whooper Swans Fecal Microbiota.

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Zhao, Na; Wang, Supen; Li, Hongyi; Liu, Shelan; Li, Meng; Luo, Jing; Su, Wen; He, Hongxuan

2018-01-01

The migration of wild birds plays an important role in the transmission and spread of H5 highly pathogenic avian influenza (HPAI) virus, posing a severe risk to animal and human health. Substantial evidence suggests that altered gut microbial community is implicated in the infection of respiratory influenza virus. However, the influence of H5N1 infection in gut microbiota of migratory birds remains unknown. In January 2015, a novel recombinant H5N1 virus emerged and killed about 100 migratory birds, mainly including whooper swans in Sanmenxia Reservoir Area of China. Here, we describe the first fecal microbiome diversity study of H5N1-infected migratory birds. By investigating the influence of H5N1 infection on fecal bacterial communities in infected and uninfected individuals, we found that H5N1 infection shaped the gut microbiota composition by a difference in the dominance of some genera, such as Aeromonas and Lactobacillus . We also found a decreased α diversity and increased β diversity in infectious individuals. Our results highlight that increases in changes in pathogen-containing gut communities occur when individuals become infected with H5N1. Our study may provide the first evidence that there are statistical association among H5N1 presence and fecal microbiota compositional shifts, and properties of the fecal microbiota may serve as the risk of gut-linked disease in migrates with H5N1 and further aggravate the disease transmission.

Neurovirulence of H5N1 infection in ferrets is mediated by multifocal replication in distinct permissive neuronal cell regions.

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Jennifer R Plourde

Full Text Available Highly pathogenic avian influenza A (HPAI, subtype H5N1, remains an emergent threat to the human population. While respiratory disease is a hallmark of influenza infection, H5N1 has a high incidence of neurological sequelae in many animal species and sporadically in humans. We elucidate the temporal/spatial infection of H5N1 in the brain of ferrets following a low dose, intranasal infection of two HPAI strains of varying neurovirulence and lethality. A/Vietnam/1203/2004 (VN1203 induced mortality in 100% of infected ferrets while A/Hong Kong/483/1997 (HK483 induced lethality in only 20% of ferrets, with death occurring significantly later following infection. Neurological signs were prominent in VN1203 infection, but not HK483, with seizures observed three days post challenge and torticollis or paresis at later time points. VN1203 and HK483 replication kinetics were similar in primary differentiated ferret nasal turbinate cells, and similar viral titers were measured in the nasal turbinates of infected ferrets. Pulmonary viral titers were not different between strains and pathological findings in the lungs were similar in severity. VN1203 replicated to high titers in the olfactory bulb, cerebral cortex, and brain stem; whereas HK483 was not recovered in these tissues. VN1203 was identified adjacent to and within the olfactory nerve tract, and multifocal infection was observed throughout the frontal cortex and cerebrum. VN1203 was also detected throughout the cerebellum, specifically in Purkinje cells and regions that coordinate voluntary movements. These findings suggest the increased lethality of VN1203 in ferrets is due to increased replication in brain regions important in higher order function and explains the neurological signs observed during H5N1 neurovirulence.

Influenza Risk Management: Lessons Learned from an A(H1N1) pdm09 Outbreak Investigation in an Operational Military Setting

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2013-07-10

Olalla Peralta P, et al.. Pandemic Influenza (H 1 N 1) 2009 Outbreak in a Military Academy: start of community circulation in Spain. Rev Esp Salud ... Publica 84(5):597-607 5. Kapp L, Jansen DJ (2009) The role of the Department of Defense during a flu pandemic. Washington (DC): CRS Report for Congress

Students in Differential Equations and Epidemiology Model a Campus Outbreak of pH1N1

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Meredith L. Greer

2012-08-01

Full Text Available We describe a semester-long collaboration between a mathematics class and a biology class. Students worked together to understand and model the trajectory of the pandemic H1N1, pH1N1, outbreak across campus in fall 2009. Each course had about 30 students and was an upper-level elective for majors. Some mathematics students had taken no college-level biology, and some biology students had taken no college-level mathematics. All students had taken at least three quantitative courses, so they had some experience working with data. Our goals were to allow students to work with and model a real data set that affected them personally, to explore how the outbreak spread within our small campus, and for students to share their areas of expertise. This project created opportunities for synthesis and evaluation.  

A comparative evaluation of feathers, oropharyngeal swabs, and cloacal swabs for the detection of H5N1 highly pathogenic avian influenza virus infection in experimentally infected chickens and ducks.

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Nuradji, Harimurti; Bingham, John; Lowther, Sue; Wibawa, Hendra; Colling, Axel; Long, Ngo Thanh; Meers, Joanne

2015-11-01

Oropharyngeal and cloacal swabs have been widely used for the detection of H5N1 highly pathogenic avian Influenza A virus (HPAI virus) in birds. Previous studies have shown that the feather calamus is a site of H5N1 virus replication and therefore has potential for diagnosis of avian influenza. However, studies characterizing the value of feathers for this purpose are not available, to our knowledge; herein we present a study investigating feathers for detection of H5N1 virus. Ducks and chickens were experimentally infected with H5N1 HPAI virus belonging to 1 of 3 clades (Indonesian clades 2.1.1 and 2.1.3, Vietnamese clade 1). Different types of feathers and oropharyngeal and cloacal swab samples were compared by virus isolation. In chickens, virus was detected from all sample types: oral and cloacal swabs, and immature pectorosternal, flight, and tail feathers. During clinical disease, the viral titers were higher in feathers than swabs. In ducks, the proportion of virus-positive samples was variable depending on viral strain and time from challenge; cloacal swabs and mature pectorosternal feathers were clearly inferior to oral swabs and immature pectorosternal, tail, and flight feathers. In ducks infected with Indonesian strains, in which most birds did not develop clinical signs, all sampling methods gave intermittent positive results; 3-23% of immature pectorosternal feathers were positive during the acute infection period; oropharyngeal swabs had slightly higher positivity during early infection, while feathers performed better during late infection. Our results indicate that immature feathers are an alternative sample for the diagnosis of HPAI in chickens and ducks. © 2015 The Author(s).

Performance of clinical signs in poultry for the detection of outbreaks during the avian influenza A (H7N7) epidemic in The Netherlands in 2003.

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Elbers, Armin R W; Koch, Guus; Bouma, Annemarie

2005-06-01

The aim of this study was to make an inventory of the clinical signs of high-pathogenicity avian influenza (HPAI), to facilitate the development of an operational syndrome-reporting system (SRS) in The Netherlands as an early warning system for HPAI outbreaks. A total of 537 poultry flocks (240 infected and 297 non-infected) with a clinical suspicion of an infection with HPAI virus were investigated with respect to the clinical signs observed. Standardized reports were analysed with respect to observed clinical signs in the flocks. Various poultry types were distinguished. In infected commercial flocks with egg-producing chickens, the presence of increased mortality, apathy, coughing, reduction in normal vocalization, or pale eggs appeared to be overall the most sensitive indicators to detect a HPAI outbreak, matching a sensitivity of 99% with a specificity of 23%. In infected turkey flocks, the presence of apathy, decreased growth performance, reduction of normal vocalization, swollen sinuses, yawning, huddling, mucosal production from the beak, or lying down with an extended neck appeared to be overall the most sensitive indicators to detect a HPAI outbreak, matching a sensitivity of 100% with a specificity of 79%. In infected backyard/hobby flocks, increased mortality or swollen head appeared to be overall the most sensitive indicators of a HPAI outbreak, matching a sensitivity of 100% with a specificity of 26%. These results indicate that there is a solid basis for the choice of using increased mortality in the operational SRS in The Netherlands as an early warning system for HPAI outbreaks. The presence of apathy, specifically for turkeys, should be added to the SRS as an indicator.

Live bird markets of Bangladesh: H9N2 viruses and the near absence of highly pathogenic H5N1 influenza.

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Nicholas J Negovetich

2011-04-01

Full Text Available Avian influenza surveillance in Bangladesh has been passive, relying on poultry farmers to report suspected outbreaks of highly pathogenic H5N1 influenza. Here, the results of an active surveillance effort focusing on the live-bird markets are presented. Prevalence of influenza infection in the birds of the live bird markets is 23.0%, which is similar to that in poultry markets in other countries. Nearly all of the isolates (94% were of the non-pathogenic H9N2 subtype, but viruses of the H1N2, H1N3, H3N6, H4N2, H5N1, and H10N7 subtypes were also observed. The highly pathogenic H5N1-subtype virus was observed at extremely low prevalence in the surveillance samples (0.08%, and we suggest that the current risk of infection for humans in the retail poultry markets in Bangladesh is negligible. However, the high prevalence of the H9 subtype and its potential for interaction with the highly pathogenic H5N1-subtype, i.e., reassortment and attenuation of host morbidity, highlight the importance of active surveillance of the poultry markets.

Establishing a laboratory network of influenza diagnosis in Indonesia: an experience from the avian flu (H5N1 outbreak

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Setiawaty V

2012-08-01

Full Text Available Vivi Setiawaty, Krisna NA Pangesti, Ondri D SampurnoNational Institute of Health Research and Development, Ministry of Health, the Republic of Indonesia, Jakarta, IndonesiaAbstract: Indonesia has been part of the global influenza surveillance since the establishment of a National Influenza Center (NIC at the National Institute of Health Research and Development (NIHRD by the Indonesian Ministry of Health in 1975. When the outbreak of avian influenza A (H5N1 occurred, the NIC and US Naval Medical Research Unit 2 were the only diagnostic laboratories equipped for etiology confirmation. The large geographical area of the Republic of Indonesia poses a real challenge to provide prompt and accurate diagnosis nationally. This was the main reason to establish a laboratory network for H5N1 diagnosis in Indonesia. Currently, 44 laboratories have been included in the network capable of performing polymerase chain reaction testing for influenza A. Diagnostic equipment and standard procedures of biosafety and biosecurity of handling specimens have been adopted largely from World Health Organization recommendations.Keywords: influenza, laboratory, networking

Avian influenza H5N1 viral and bird migration networks in Asia

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Tian, Huaivu; Zhou, Sen; Dong, Lu; Van Boeckel, Thomas P.; Cui, Yujun; Newman, Scott H.; Takekawa, John Y.; Prosser, Diann J.; Xiao, Xiangming; Wu, Yarong; Cazelles, Bernard; Huang, Shanqian; Yang, Ruifu; Grenfell, Bryan T.; Xu, Bing

2015-01-01

The spatial spread of the highly pathogenic avian influenza virus H5N1 and its long-term persistence in Asia have resulted in avian influenza panzootics and enormous economic losses in the poultry sector. However, an understanding of the regional long-distance transmission and seasonal patterns of the virus is still lacking. In this study, we present a phylogeographic approach to reconstruct the viral migration network. We show that within each wild fowl migratory flyway, the timing of H5N1 outbreaks and viral migrations are closely associated, but little viral transmission was observed between the flyways. The bird migration network is shown to better reflect the observed viral gene sequence data than other networks and contributes to seasonal H5N1 epidemics in local regions and its large-scale transmission along flyways. These findings have potentially far-reaching consequences, improving our understanding of how bird migration drives the periodic reemergence of H5N1 in Asia.

Low-pathogenic influenza A viruses in North American diving ducks contribute to the emergence of a novel highly pathogenic influenza A(H7N8) virus

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Xu, Yifei; Ramey, Andrew M.; Bowman, Andrew S; DeLiberto, Thomas J.; Killian, Mary Lea; Krauss, Scott; Nolting, Jacqueline M.; Torchetti, Mia Kim; Reeves, Andrew B.; Webby, Richard J.; Stallknecht, David E.; Wan, Xiu-Feng

2017-01-01

Introductions of low-pathogenic avian influenza (LPAI) viruses of subtypes H5 and H7 into poultry from wild birds have the potential to mutate to highly pathogenic avian influenza (HPAI) viruses, but such viruses' origins are often unclear. In January 2016, a novel H7N8 HPAI virus caused an outbreak in turkeys in Indiana, USA. To determine the virus's origin, we sequenced the genomes of 441 wild-bird origin influenza A viruses (IAVs) from North America and subjected them to evolutionary analyses. The results showed that the H7N8 LPAI virus most likely circulated among diving ducks in the Mississippi flyway during autumn 2015 and was subsequently introduced to Indiana turkeys, in which it evolved high pathogenicity. Preceding the outbreak, an isolate with six gene segments (PB2, PB1, PA, HA, NA, and NS) sharing >99% sequence identity with those of H7N8 turkey isolates was recovered from a diving duck sampled in Kentucky, USA. H4N8 IAVs from other diving ducks possessed five H7N8-like gene segments (PB2, PB1, NA, MP, and NS; >98% sequence identity). Our findings suggest that viral gene constellations circulating among diving ducks can contribute to the emergence of IAVs that affect poultry. Therefore, diving ducks may serve an important and understudied role in the maintenance, diversification, and transmission of IAVs in the wild-bird reservoir.

Clinical and epidemiologic characteristics of an outbreak of novel H1N1 (swine origin) influenza A virus among United States military beneficiaries.

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Crum-Cianflone, Nancy F; Blair, Patrick J; Faix, Dennis; Arnold, John; Echols, Sara; Sherman, Sterling S; Tueller, John E; Warkentien, Tyler; Sanguineti, Gabriela; Bavaro, Mary; Hale, Braden R

2009-12-15

A novel swine-origin influenza A (H1N1) virus was identified in March 2009 and subsequently caused worldwide outbreaks. The San Diego region was an early focal point of the emerging pandemic. We describe the clinical and epidemiologic characteristics of this novel strain in a military population to assist in future outbreak prevention and control efforts. We performed an epidemiologic evaluation of novel H1N1 virus infections diagnosed in San Diego County among 96,258 local US military beneficiaries. The structured military medical system afforded the ability to obtain precise epidemiologic information on the impact on H1N1 virus infection in a population. The novel H1N1 virus was confirmed using real-time reverse transcriptase polymerase chain reaction (rRT-PCR). From 21 April through 8 May 2009, 761 patients presented with influenza-like illness and underwent rRT-PCR testing. Of these patients, 97 had confirmed novel H1N1 virus infection, with an incidence rate of 101 cases per 100,000 persons. The median age of H1N1 patients with H1N1 virus infection was 21 years (interquartile range, 15-25 years). Fever was a universal symptom in patients with H1N1 virus infection; other symptoms included cough (present in 96% of patients), myalgia or arthralgia (57%), and sore throat (51%). Sixty-eight (70%) of our patients had an identifiable epidemiologic link to another confirmed patient. The largest cluster of cases of H1N1 virus infection occurred on a Navy ship and involved 32 (8%) of 402 crew members; the secondary attack rate was 6%-14%. The rapid influenza testing that was used during this outbreak had a sensitivity of 51% and specificity of 98%, compared with rRT-PCR. Only 1 patient was hospitalized, and there were no deaths. A novel H1N1 influenza A virus caused a significant outbreak among military beneficiaries in San Diego County, including a significant cluster of cases onboard a Navy ship. The outbreak described here primarily affected adolescents and young