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Avian Influenza Daily Digest
September 4, 2008 14:00 GMT
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Article Summaries ...
Regional Reporting and Surveillance
Indonesia Reported Only 30% of Avian Influenza Cases to International Health Organizations
9/4/08 Contributed by multiple sources--According to the Research and Technology Ministry, Indonesia only reported 30% of avian influenza cases to international health organizations. Indonesia does not report bird die-offs and has trouble detecting human cases. Reportedly, the official believed that this challenge came mostly from the public?s reluctance to report avian influenza cases. Weak surveillance and incomplete as well as inaccurate data further prohibit timely reporting. The official also claimed a decline in avian influenza cases for 2008.
Regional Reporting and Surveillance
Science and Technology
Environmental Factors Contributing to the Spread of H5N1 Avian Influenza in Mainland China
9/3/08 PubMed--Full Text--Background--Since late 2003, highly pathogenic avian influenza (HPAI) outbreaks caused by infection with H5N1 virus has led to the deaths of millions of poultry and more than 10 thousands of wild birds, and as of 18-March 2008, at least 373 laboratory-confirmed human infections with 236 fatalities, have occurred. The unrestrained worldwide spread of this disease has caused great anxiety about the potential of another global pandemic. However, the effect of environmental factors influencing the spread of HPAI H5N1 virus is unclear.
AI Research
Laboratory investigation of the first suspected human cases of infection with avian influenza A(H5N1) virus in Bulgaria
9/3/08 PubMed--[Abstract]--Department of Virology, National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria. In the end of 2005 and the beginning of 2006, avian influenza A(H5N1) virus caused outbreaks among domestic poultry and was isolated from wild swans in many European countries, including Bulgaria. Between January and March 2006, samples were collected from 26 patients who had been in close contact with ill or dead birds and developed a subsequent respiratory illness. The testing took place at the National Laboratory of Influenza in Sofia.
AI Research
Virologists working on DNA vaccines for H5N1 virus
/4/08 China Post--Scientists at the Academia Sinica are working on developing some novel vaccines for the avian influenza H5N1 virus and DNA-based vaccines have proven to be capable of providing protection for various H5N1 strains, researchers at the institution said yesterday.
Vaccines
University of Delaware poultry researchers win $5M USDA grant
9/4/08 Cape Gazette--Researchers at the University of Delaware will continue avian influenza research through a $5 million dollar grant from the U.S. Department of Agriculture?s Cooperative State Research, Education and Extension Service. The grant, to be spent over three years, renews the Avian Influenza Coordinated Agricultural Project, a partnership between the University of Maryland at College Park and 17 other leading institutions that are researching avian influenza across the United States, including the University of Delaware.
AI Research
Glaxo offers corporate plan for its flu drug
9/3/08 Reuters--GlaxoSmithKline released a new plan on Wednesday for companies to stockpile its influenza drug Relenza in case of a pandemic. The plan gives businesses two options: to buy Relenza now at a discount with free storage, or to pay an annual fee to reserve the flu drug for future purchase at a capped rate.
Antivirals
Full Text of Articles follow ...
Regional Reporting and Surveillance
Indonesia Reported Only 30% of Avian Influenza Cases to International Health Organizations
9/4/08 Contributed by multiple sources--According to the Research and Technology Ministry, Indonesia only reported 30% of avian influenza cases to international health organizations. Indonesia does not report bird die-offs and has trouble detecting human cases. Reportedly, the official believed that this challenge came mostly from the public?s reluctance to report avian influenza cases. Weak surveillance and incomplete as well as inaccurate data further prohibit timely reporting. The official also claimed a decline in avian influenza cases for 2008.
An official from the National Committee for Avian Influenza Control and Pandemic Preparedness, as reported by a local source, also noted that between 2003 and 2007, avian influenza has spread to 31 out of 33 provinces, thus turning these provinces into endemic areas for this virus and placing a "massive burden" on Indonesia?s economy.
Article URL(s)
http://www.banjarmasinpost.co.id/content/view/49716/323/
http://news.okezone.com/index.php/ReadStory/2008/09/04/1/142899/indonesia-hanya-laporkan-30-kasus-flu-burung
AI Research
Environmental Factors Contributing to the Spread of H5N1 Avian Influenza in Mainland China
9/3/08 PubMed--Full Text--Background--Since late 2003, highly pathogenic avian influenza (HPAI) outbreaks caused by infection with H5N1 virus has led to the deaths of millions of poultry and more than 10 thousands of wild birds, and as of 18-March 2008, at least 373 laboratory-confirmed human infections with 236 fatalities, have occurred. The unrestrained worldwide spread of this disease has caused great anxiety about the potential of another global pandemic. However, the effect of environmental factors influencing the spread of HPAI H5N1 virus is unclear.
Methodology/Principal Findings
A database including incident dates and locations was developed for 128 confirmed HPAI H5N1 outbreaks in poultry and wild birds, as well as 21 human cases in mainland China during 2004?2006. These data, together with information on wild bird migration, poultry densities, and environmental variables (water bodies, wetlands, transportation routes, main cities, precipitation and elevation), were integrated into a Geographical Information System (GIS). A case-control design was used to identify the environmental factors associated with the incidence of the disease. Multivariate logistic regression analysis indicated that minimal distance to the nearest national highway, annual precipitation and the interaction between minimal distance to the nearest lake and wetland, were important predictive environmental variables for the risk of HPAI. A risk map was constructed based on these factors.
Conclusions/Significance
Our study indicates that environmental factors contribute to the spread of the disease. The risk map can be used to target countermeasures to stop further spread of the HPAI H5N1 at its source.
Top
Abstract
>Introduction
Results
Discussion
Materials and Methods
References
Introduction
The H5N1 subtype of the influenza A virus was initially detected in poultry on a farm of Scotland, UK, in 1959 [1]. The highly pathogenic avian influenza (HPAI) virus reappeared in 1997 and caused an outbreak in chicken farms and live bird markets in Hong Kong, where 18 human cases were reported with 6 deaths [2]. The recent chain of outbreaks caused by H5N1 started among poultry in South Korea in December 2003, and has affected 61 countries in Asia, the Middle East, Africa and Europe leading to the deaths of millions of poultry and more than 10 thousands of wild birds [3], [4]. Even worse, the HPAI H5N1 virus appears to have gained ability to cross the species barrier and induce severe disease and death in humans as well as other mammals.
As of 18-March 2008, there have been 373 laboratory-confirmed human infections, of which 236 have died [5]. The worldwide spread of the disease is providing more opportunities for viral re-assortment within a host (genetic shift) and mutation over time (genetic drift). These factors may lead to a viral strain that is more efficient at person-to-person transmission, raising the potential for another pandemic to occur [6]?[9]. Since January 2004, HPAI H5N1 outbreaks in poultry and wild birds, and occasional trans-species transmission to humans have been reported throughout mainland China [5], [10]. Surveillance studies suggested that poultry movement and wild bird migration may have contributed to such a quick spread [7], [11], [12]. However, the processes, including environmental factors, influencing the spread of HPAI H5N1 virus are not clearly understood.
In this study, we explore environmental factors associated with such outbreaks in mainland China to provide essential information for developing effective and appropriate countermeasures.
Top
Abstract
Introduction
>Results
Discussion
Materials and Methods
References
Results
Since the emergence of HPAI H5N1 infections in mainland China in January 2004, a total of 128 outbreaks of HPAI H5N1, spanning a large geographic area of mainland China, has occurred in poultry and wild birds at the village/township level in 26 of 31 provinces, municipalities or autonomous regions by the end of 2006 [10]. The spatial distributions of HPAI H5N1 outbreaks in poultry and wild birds, and human cases in mainland China were displayed in the thematic map (Figure 1). The background of the map was the poultry density. The generalized migration routes of birds were overlapped on the map.
Figure 1 Figure 1
Spatial distribution of HPAI H5N1 outbreaks in domestic poultry and wild birds and human cases in mainland China.
In a case-control study, minimal distances to the nearest lake, wetland, national highway and main city, as well as annual precipitation appeared to be significantly associated factors in the univariate analysis (Table 1). Multivariate logistic regression demonstrated that three variables, minimal distance to the nearest national highway, annual precipitation and the interaction between minimal distance to the nearest lake and wetland, were significantly associated with HPAI H5N1 outbreaks (Table 1). Goodness of fit for the logistic regression model was evaluated using Hosmer-Lemeshow test, showing a high risk discrimination between outbreak sites and ?control? areas (X2 = 4.305, P = 0.829).
Table 1 Table 1
The association between H5N1 outbreaks and influential factors by logistic regression analysis.
We have also investigated possible overestimation of effects due to clustering of neighboring outbreaks. Within clusters, transmission of H5N1 from one location to another could have occurred directly, instead of through the investigated environmental factors. Using the criterion of a distance <20 km and a time-interval <3 weeks, we could identify 6 clusters in a total of 30 outbreaks. We have repeated the multivariate logistic regression using only one randomly selected outbreak site from each cluster (i.e., 104 cases and 520 controls), but this did not lead to significantly different results. The adjusted OR and P-value for the three factors, minimal distance to the nearest national highway, annual precipitation and the interaction between minimal distance to the nearest lake and wetland, were 0.825 (P = 0.005), 0.915 (P = 0.001), and 0.970 (P<0.001) respectively.
Based on the predictive model derived from the logistic regression analysis, a predictive risk map of HPAI H5N1 infections was established for mainland China by GIS technologies (Figure 2). On the risk map, the locations of HPAI H5N1 outbreaks in poultry from January of 2007 to March 13, 2008 were also plotted (8 outbreaks). The overlapping analysis revealed that 87.5% (7/8) of outbreaks of HPAI H5N1 in poultry occurred in the predictive highest or high-risk areas (Figure 2).
Figure 2 Figure 2
Predictive risk map of HPAI H5N1 outbreaks in birds.
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Abstract
Introduction
Results
>Discussion
Materials and Methods
References
Discussion
The results of our case-control study demonstrate that the interaction between minimal distance to the nearest lake and wetland minimal distance to the nearest national highway, and the annual average precipitation are the principal environmental variables contributing to the spread of HPAI H5N1 virus in mainland China. These findings indicate that bird populations in close proximity to a body of water are in danger of becoming infected, and provide further evidence for the role of waterfowl in the transmission of avian influenza. HPAI is mainly characterized by a quick spread and a high mortality rate in poultry. However, except for some species [13], waterfowl are typically asymptomatic reservoirs for H5N1 [14], perhaps shedding virus through their salivary and nasal secretions and feces into bodies of water in which they are inhabiting [11]. It is estimated that the virus can survive in water at 22°C for up to 4 days and up to 30 days at 0°C [15]. People may unconsciously take the virus to a body of water from contaminated surfaces or infected birds. Birds and other animals also may transport the virus on their feathers or fur to a water source after coming into contact with an infected animal or contaminated surface on a farm. The spread of the virus is facilitated when the body of water, such as a lake, is stagnant and adjacent to a farm or community [16]. Interestingly, as the precipitation in a region increases, the risk of HPAI H5N1 outbreaks is reduced. One explanation for this result may be that lower precipitation levels may lead to a higher concentration of birds in a reduced number of wetlands, thus increasing the chances of bird becoming infected through contact with the virus.
Proximity to national highway is another risk factor contributing to HPAI infection. National highways in mainland China are funded and constructed by the central government and are vital connections between provinces, without collection of toll. As there are many restrictions on railway transportation of poultry in mainland China [17], and tolls on freeways are quite high, national highways are usually top-priority to transport poultry and their products throughout the country. During long-distant transportation, a variety of birds and animals from various origins are caged on top of each other, perhaps providing an easy way of cross-infection of avian influenza. In addition, many open live poultry markets are established along or near the national highways, which may further increase the chance of virus transmission. These findings suggest that trade and mechanical movement of poultry may facilitate spread of HPAI H5N1 virus, supporting laboratory evidence as demonstrated by Li et al. [9].
The logistic regression analysis in the study demonstrates that the risk of HPAI H5N1 infections are not increased with the poultry density, as is usually presumed. This may due to the fact that poultry, especially chickens in the areas with high population densities, are usually bred in industrialized farms with good animal husbandry practices and properly vaccinated [18]. Although the importance as an ecological reservoir is uncertain, migratory birds may spread H5N1 viruses to new geographic regions. Usually migratory birds cannot fly the full distance to their annual migratory destination. Instead, they usually interrupt their migration to rest and refuel [19]. Avian influenza may be spread between wild and domestic birds when migratory birds search for food, water and shelter. The infected wild birds can carry the influenza virus for long distances during migration [20]. Migratory birds are loyal to their annual migratory destinations and their stopover points, such as water bodies, wetlands and forests [21]. As wetlands and forests are destroyed however, due to increased human activities, especially land utilization practices, migratory birds may be forced to search for shelter and food in other places such as farms. This may result in increases contact between wild and domestic birds, thus facilitating the transmission of the virus to domestic bird populations.
In conclusion, the analyses of the spatial distribution and underlying environmental determinants reveal that the spread of the HPAI H5N1 is probably taking place at two different but interlinked patterns. Transportation of poultry and their products along highways may contribute to the long-distant national wide spread of the disease. Contacts with infected birds, trade and mechanical movement of poultry may be responsible for local transmission. The two spread patterns can exist simultaneously, and HPAI H5N1 outbreaks can take place near national highways, near relatively stagnant bodies of water such as lakes and wetlands, and in particular when there is reduced rainfall. The predictive risk map of HPAI H5N1 infections established for mainland China on basis of the above contributing factors may be useful for identifying the areas where surveillance, vaccination and other preventive interventions should be targeted.
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Abstract
Introduction
Results
Discussion
>Materials and Methods
References
Materials and Methods
Data collection and management
The data on HPAI H5N1 outbreaks in animals were obtained from monthly reports, the official veterinary bulletins of the Ministry of Agriculture of China and from updates on HPAI in animals from the World Organization for Animal Health (OIE) [3], [22]. All the outbreaks were confirmed with laboratory based virological methods and officially reported in mainland China.
We developed a database including the information on the incident dates (rather than the dates of reporting) and locations of outbreak in birds. The information on human cases with H5N1 infection in mainland China was also included in the database. Each of the HPAI H5N1 outbreaks in birds, as well as human infections, were geo-coded at the village/township level and linked to a digital map at the scale of 1[ratio]100,000 using geographical information system (GIS) technologies. Point-type information (single pair coordinates) was created for each outbreak site, while line-type information was generated for migration routes of migratory birds, based on detailed bird banding records from mainland China [23]. Polygon-type information for water bodies were derived from digital maps. The three-type information was overlapped for analyses in our study. Water bodies included lakes with a surface AREA ?1.0 km2, reservoirs having a surface area ?1.0 km2 and both were used as polygon-type map layers. In addition, information on transportation, main cities and elevation were directly obtained from digital maps (provided by the coauther Dr. Peng Gong from State Key Laboratory of Remote Sensing Science). According to the definition suggested by U.S. Fish and Wildlife Service [24], [25], wetlands stated in the current study only included swamps, water meadows, wading lakes with a surface ?1.0 km2, and excluded rivers, reservoirs and deep lakes. The data on wetlands were obtained from the National Geographical Resourse Center, which were derived from wetland census data collected in mainland China. These data were digitized as point-type information.
Transportation including railways, freeways and national highways were used as line-type information. Main cities included 31 provincial capitals and 305 prefecture-level cities in mainland China and were used as point-type information. The layer of elevation was used as line-type information and was preprocessed to convert it to a raster-type layer for this study. The raster-type map layer of precipitation extrapolated by the kriging technique using 700 weather stations in mainland China was collected from the Institute of Geographical Sciences and Natural Resources Research, Chinese Academy of Sciences. Poultry density information was obtained from the FAO [26], which was a raster-type layer and was as the predicted poultry density, corrected for unsuitability and adjusted to match observed totals.
GIS spatial analysis
The spatial distribution of outbreaks in birds and human cases was studied through overlapping analysis. A thematic map was established on which the poultry density was taken as the background. To understand the role of bird migration in the spread of H5N1 virus, map layer of bird migration was created and overlapped on the map of spatial distribution of outbreaks in birds and human cases.
Analysis of environmental factors associated with H5N1 outbreaks
A case-control study design was used to clarify the environmental factors associated with the spread of HPAI H5N1. The 128 outbreak sites were taken as ?cases?. All other villages and townships in mainland China except for those affected by HPAI H5N1 outbreaks from 2004 to 2006, were defined as non-epidemic areas. Then 640 ?control? sites (5 controls/case) were randomly selected from the non-epizootic areas in mainland China and then were geo-coded (see Figure 3 for the location of cases and controls). Eight environmental factors (bodies of water, wetlands, transportation routes, migration routes, main cities, precipitation, elevation and poultry density) involving twelve variables were considered in the study. The minimum distances to the nearest bodies of water including lakes, reservoirs and rivers, as the polygon-type information, were measured using a proximity function of spatial analysis in such an algorithm that the minimal distance from each case and control site to its nearest water body edge was calculated. The minimal distance from each ?case/control? site to its nearest points or lines was calculated, using point-type or line-type information (i.e., wetlands, transportation routes including railways, freeways and national highways, migration routes and main cities). Furthermore, using a zonal statistical calculation technique, an 8 km mean buffer zone (the outbreak area of 3 km plus risk area of 5 km around the outbreak site) was calculated for the variables, annual precipitation, elevation and poultry density (as raster-type map layers), for each case and control site.
Figure 3 Figure 3
Spatial random sampling for the case-control design.
Statistical analyses were performed using the Statistical Package for Social Sciences (SPSS Inc, Chicago, IL, USA). Unconditional logistic regression was performed, and odds ratios (ORs), their 95% confidence intervals (CIs) and P-values were estimated using maximum likelihood methods. ORs of the variables involving minimal distances to the nearest body of water, wetlands, transportation routes, bird migration routes and main cities were calculated for a ten-kilometer difference. However, for annual precipitation for a 100-millimeter difference, elevation for a 100-meter difference and poultry density for 1000-bird difference per square kilometer, ORs were estimated respectively. Univariate analyses were conducted to examine the effect of each variable separately. Quadratic and logarithmic transformations of each variable were also tested, but these did not perform significantly better than a linear association for any of the variables. Multivariate analysis was then performed using the variables with P-value of <0.1 from the univariate analyses as covariates. The possible interactions between each covariate were also included in the multivariate analysis. The colinearity between covariate in the case control study was quantitatively assessed. Correlations between minimal distances to the nearest lake, minimal distance to the nearest wetland and minimal distance to the nearest river were identified. Models were also optimized by comparing the ?2 log likelihood and Hosmer-Lemeshow goodness of fit when correlated variables were added or removed. It was discovered that more accurate models could be derived by removing the variable of minimal distance to the nearest river. A P-value <0.05 was considered statistically significant by using backward-LR method. Goodness of fit for the logistic regression model was evaluated by using the Hosmer-Lemeshow goodness of fit test.
To predict the risks of HPAI H5N1 occurrence, a grid map was created using GIS techniques. The values of the above predictive variables were determined for each grid with an area of 100 km2 (10×10 km) based on the predictive model derived from the multivariate logistic regression analysis. By interlinking all the grids, a predictive risk map of HPAI H5N1 infections was established for mainland China. The risk of HPAI occurrence for each grid was calculated and classified as the highest risk, high risk, medium risk and low risk according to quartile levels for predicted prevalence in the predictive map.
Footnotes
Competing Interests: The authors have declared that no competing interests exist.
Funding: This study was supported by grants from the National Science Fund for Distinguished Young Scholars (No. 30725032), National Natural Science Foundation of China (No. 30590374) and the Commission of the European Community, as part of the project ?Effective and Acceptable Strategies for the Control of SARS and New Emerging Infections in China and Europe? (No. 003824). The founders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Abstract
Introduction
Results
Discussion
Materials and Methods
>References
References
1.
Anonym. Asian H5N1 still going strong at 10 years old. Lencet Infect Dis. 2007;7:175.
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De Jong JC, Claas EC, Osterhaus ADME, Webster RG, Lim WL. A pandemic warning? Nature. 1997;389:554. [PubMed]
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World Organization for Animal Health. Summary of immediate notifications and follow-ups (highly pathogenic avian influenza). 2008. Available: http://www.oie.int/wahid-prod/public.phppagedisease_immediate_summarydisease_id15. Accessed 25 March 2008.
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World Organization for Animal Health. Avian influenza: Facts & figures. 2008. Available: http://www.oie.int/eng/info_ev/en_AI_factoids_2.htm. Accessed 25 March 2008.
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World Health Organization. Cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO. 2008. Available: http://www.who.int/csr/disease/avian_influenza/country/cases_table_2008_03_18/en/index.html, 2008). Accessed 25 March 2008.
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Chen H, Smith GJD, Zhang SY, Qin K, Wang J, et al. Avian flu: H5N1 virus outbreak in migratory waterfowl. Nature. 2005;436:191?192. [PubMed]
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Chen H, Li Y, Li Z, Shi J, Shinya K, et al. Properties and dissemination of H5N1 viruses isolated during an influenza outbreak in migratory waterfowl in western China. J Virol. 2006;80:5976?5983. [PubMed]
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Ferguson NM, Cummings DA, Cauchemez S, Fraser C, Riley S, et al. Strategies for containing an emerging influenza pandemic in Southeast Asia. Nature. 2005;437:209?214. [PubMed]
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Li KS, Guan Y, Wang J, Smith GJ, Xu KM, et al. Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Aria. Nature. 2004;430:209?213. [PubMed]
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Chen H, Smith GJD, Li KS, Wang J, Fan XH, et al. Establishment of multiple sublineages of H5N1influenza virus in Asia: Implications for pandemic control. Proc Natl Acad Sci USA. 2006;103:2845?2850. [PubMed]
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Liu C, Lin S, Chen Y, Lin KC, Wu TJ, et al. Temperature drops and the onset of severe avian influenza A H5N1 virus outbreaks. PLoS ONE. 2007;2:e191. [PubMed]
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Liu J, Xiao H, Lei F, Zhu Q, Qin K, et al. Highly pathogenic H5N1 influenza virus infection in migratory birds. Science. 2005;309:1206. [PubMed]
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Harder B. When flu flies the coop: A pandemic threatens. Science News. 2005;168:171.
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World Health Organization. Waterborne zoonoses. 2004. Available: www.who.int/water_sanitation_health/diseases/zoonoses.pdf. Accessed 27 March 2008.
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The Ministry of Railways, China. The regulation of transportation by railroad for fresh and live cargoes. 1982. Availale: http://data.laweach.com/content_497559.html. Accessed 25 March 2008.
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World Health Organization. Direct and indirect factors facilitating the spread of the Avian Influenza virus. 2006. Available: http://www.searo.who.int/LinkFiles/Publications_and_Documents_factors.pdf. Accessed 25 March 2008.
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Alerstam, T.; Lindstrom, A. Berlin: Spring-Verlag; 1990. Optimal bird migration: The relative importance of time, energy and safety. Bird migration: Physiology and ecophysiology. pp. 331?351.
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Hoyo, JD.;Elliot, A.; Sartagal, J. Barcelona: Lynx Edicions; 1996. Hoatzin to Auks. Handbook of the birds of the World. Vols. 1 and 3.
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Ministry of Agriculture, China. Reporting on animal infectious diseases. 2007. Available: http://www.agri.gov.cn/ztzl/fzqlg/yqfb. Accessed 12 October 2007.
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Zhang, F.; Yang, R. Beijing: China Forest Press; 1997. Bird Migration in China. p. 46.
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Shaw, SP.; Fredine, CG. Washington, D.C.: U.S. Fish and Wildlife Service Circular 39; 1956. Wetlands of the United States?Their extent and their value to waterfowl and other wildlife. p. 67.
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AI Research
Laboratory investigation of the first suspected human cases of infection with avian influenza A(H5N1) virus in Bulgaria
9/3/08 PubMed--[Abstract]--Department of Virology, National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria.
In the end of 2005 and the beginning of 2006, avian influenza A(H5N1) virus caused outbreaks among domestic poultry and was isolated from wild swans in many European countries, including Bulgaria. Between January and March 2006, samples were collected from 26 patients who had been in close contact with ill or dead birds and developed a subsequent respiratory illness. The testing took place at the National Laboratory of Influenza in Sofia.
Vaccines
Virologists working on DNA vaccines for H5N1 virus
9/4/08 China Post--Scientists at the Academia Sinica are working on developing some novel vaccines for the avian influenza H5N1 virus and DNA-based vaccines have proven to be capable of providing protection for various H5N1 strains, researchers at the institution said yesterday.
A team of researchers at Taiwan's leading academic body has also discovered that once new virus strains are found, the strains' genetic information can be incorporated into the vaccine database to produce new vaccines that can induce immunity against new strains of H5N1, one of the academics said.
The findings of the team, led by David Ho of the Rockefeller University and Chi-huey Wong of Academia Sinica's Genomics Research Center, were published on Sept. 2 in the online edition of the publication "Proceedings of the National Academy of Sciences".
The team started its research two years ago with the focus on hemagglutinin, or HA -- a type of glycoprotein molecule that can be found on the surface of all H5N1 viruses and plays a vital role in the viral infection process, according to a press release of the Academia Sinica.
After analyzing hundreds of hemagglutinin samples that were collected from various H5N1 strains, an identical gene sequence -- dubbed "Consensus HA" -- were found on all specimens.
The sequence was later genetically engineered to produce the prototype vaccines.
During experiments, lab mice that have been inoculated were found to develop immunity of various H5N1 strains, including the strains found in Vietnam, Indonesia, Turkey, and southern China.
"When infected by the Indonesian strain of H5N1, 80 percent of the subject mice survived, " said Ting-jen Rachel Cheng of the Genomics Research Center.
"Meanwhile, 100-percent survival rates were found among all mice that were exposed to the other three strains," she said.
However, DNA-based vaccines have one distinct drawback.
"Based on the experiments (and) research done by other scientists, DNA-based vaccines are prone to elicit weak immune response, " said Chen Ming- wei, a post-graduate student at National Yang-Ming University and the paper's lead author.
The team therefore decided to enhance the vaccines' effects with an electroporation device developed by Ho, Chen said, adding that the device injects the vaccine into the muscle while generating a brief electrical pulse to "push" the DNA into the cells.
"Delivered in this way, the DNA-based vaccine induced quite drastic immune responses, and protected mice against most of the avian flu strains tested," he said.
The newly developed vaccines have been transferred to the Development Center for Biotechnology -- a Taiwan-based non- profit organization -- to undergo animal safety tests, according to the Academia Sinica.
After further testing is completed by the end of 2008, the vaccine will be submitted to the U.S. Department of Health and the Food and Drug Administration as a new drug awaiting human trials. Once approved, the phase-I clinical trial in humans can be carried out.
AI Research
University of Delaware poultry researchers win $5M USDA grant
9/4/08 Cape Gazette--Researchers at the University of Delaware will continue avian influenza research through a $5 million dollar grant from the U.S. Department of Agriculture?s Cooperative State Research, Education and Extension Service. The grant, to be spent over three years, renews the Avian Influenza Coordinated Agricultural Project, a partnership between the University of Maryland at College Park and 17 other leading institutions that are researching avian influenza across the United States, including the University of Delaware.
The original grant, awarded to the University of Maryland and its partners in 2005, was used to establish a research and education project to help prevent and control avian influenza.
Jack Gelb, chairman of the department of animal and food sciences and professor of avian virology, and Eric Benson, associate professor of bioresources engineering, along with many other University of Delaware (UD) scientists, conduct research and extension programs that provide solutions and assistance to the poultry industry, a major food resource and economic driver on the Delmarva Peninsula.
Avian influenza research and outreach activities at UD are supported by the Avian Influenza Coordinated Agricultural Project (AICAP) as well as state and other federal funds. Projects include surveillance programs in commercial poultry, backyard flocks and wild birds; development of rapid diagnostic tests; emergency poultry depopulation research; in-house composting for responding to catastrophic poultry losses; efficacy of disinfectants and common chemical compounds on avian influenza virus; viral pathogenesis and vaccine evaluations; and regional, national and international technical assistance programs.
Gelb said, ?The AICAP is unique and is successful because it brings together top scientists to broadly address avian influenza challenges facing animal agriculture. It basically applies the land-grant agricultural philosophy to an important disease with clear poultry health consequences and potential human health implications.?
Benson and Gelb recently returned from a visit to the University of Puerto Rico Mayaguez - with which UD has an institutional collaborative agreement?where they spoke to representatives from industry, academia, extension, the government, and media about UD?s role in avian influenza research and emergency response on Delmarva.
?UD?s avian influenza emergency response and diagnostic programs are known throughout the world,? said Benson. ?We have worked with scientists from Turkey, India, Bulgaria, Romania and a variety of other countries as a result of our involvement in AICAP.?
In addition to UD and the University of Maryland, the institutions participating in AICAP are Virginia Tech, Auburn University, University of California-Davis, University of Georgia, U.S. Department of Agriculture-ARS-Southeast Poultry Research Laboratory, Ohio State University, Oregon State University, Texas A&M University and Western University Health Sciences.
AICAP goals include epidemiology, basic research, diagnostics, vaccines and education. Since 2005, AICAP researchers and educators have accomplished the following:
? Assembled the first continent-wide network to study the ecological and biological characteristics of avian influenza viruses isolated from wild birds
? Integrated research and education into a unique program available to a range of poultry producers
? Shown that quail can change and expand the host range of avian influenza viruses, and found that quail respiratory and intestinal tracts have human-like sialic acid receptors that could partially explain the emergence of avian influenza strains with the capacity to infect humans
? Developed a comprehensive program that has been delivered in 33 states and in Canada and Brazil to train producers and veterinarians on the depopulation and composting of flocks with avian influenza
? Developed a testing component for rapid diagnosis of avian influenza in birds
? Developed promising vaccines for mass immunization of birds.
At the recent Delaware Poultry Industry (DPI) awards ceremony, UD?s avian influenza diagnostic team was awarded a special recognition for significant contributions to the poultry industry; this was the first time that a group was awarded this honor. The University of Delaware?s Lasher Laboratory, at the Elbert N. and Ann V. Carvel Research and Education Center in Georgetown, provides ?time-sensitive diagnostic services to the poultry industry on a daily basis and helps to implement research findings.? Through these efforts, poultry industry health officials are kept abreast of emerging diseases.
Bill Satterfield, DPI?s executive director, said, ?This group of dedicated professionals has contributed greatly to poultry disease diagnostics and applied research over many years. Their individual years of service range from 3 to 22 years. During this time, under various leaders, the lab has grown from a small unit to a full-fledged, world-class poultry diagnostic facility, offering important, technologically advanced, poultry diagnostic services.?
Recognized at the event were laboratory team members Brenda Sample (22 years of service), Colby Smith (15 years), Kathy Phillips (15 years), Luanne Sullivan (5 years), and Billie Jean Wright (3yrs). The team routinely performs surveillance for avian influenza among commercial broiler chickens and backyard flocks, and tests diseased flocks.
Satterfield said, ?One of this group?s watershed moments was when the workloads peaked at an all-time high in 2004, the year Delmarva?s chicken industry encountered and successfully controlled low pathogen avian influenza. These individuals were the backbone of poultry diagnostic services on Delmarva, with the help of other colleagues in the University of Delaware and in the region. Our industry owes a great deal to this team for its talents, willingness to pitch in when necessary, and hard work over the years.?
For more information about the University of Delaware?s poultry health system and the Avian Bioscience Center visit http://ag.udel.edu/abc/index.html.
Antivirals
Glaxo offers corporate plan for its flu drug
9/3/08 Reuters--GlaxoSmithKline released a new plan on Wednesday for companies to stockpile its influenza drug Relenza in case of a pandemic. The plan gives businesses two options: to buy Relenza now at a discount with free storage, or to pay an annual fee to reserve the flu drug for future purchase at a capped rate.
"We are committed to helping employers and other business leaders prepare for an influenza pandemic and its impact on the health of their employees and the operational integrity of their organizations," Chris Viehbacher, president for North American pharmaceuticals at the company, said in a statement.
In June, rival Roche AG, which makes the flu drug Tamiflu, offered a similar plan.
Most experts agree that a pandemic of some type of influenza is certain, although no one can predict when or what strain might strike.
The main suspect is H5N1 avian influenza, which has swept through flocks of birds in Asia, Europe, the Middle East and Africa and become entrenched in ways that experts say has never happened before.
It rarely infects people but has killed 243 out of 385 people infected globally so far, according to the World Health Organization.
The WHO has recommended that countries prepare for such a pandemic, and the U.S. Health and Human Services Department has also encouraged employers to do so. Many companies are developing plans that include treating employees during a pandemic.
Several experimental vaccines are being tested against H5N1, but if a pandemic were to start, it would likely be months before vaccine production could begin to be ramped up.
Relenza, known generically as zanamivir, and Tamiflu, known generically as oseltamivir, are both used to treat seasonal influenza. Tamiflu is the drug of choice for H5N1 infection although experiments suggest Relenza would work, too.
Last month GlaxoSmithKline and its Australian partner Biota Holdings Ltd (BTA.AX: Quote, Profile, Research, Stock Buzz) settled a damages claim over Glaxo's marketing of Relenza. Glaxo recently has started to ramp up Relenza production and sales.
Roche licenses Tamiflu from California-based Gilead Sciences (GILD.O: Quote, Profile, Research, Stock Buzz).
Tamiflu, a pill, has far outsold Relenza, which is an inhaled powder. But governments recommend stockpiling both.
A new influenza drug, peramivir, is being developed by Biocryst Pharmaceuticals Inc (BCRX.O: Quote, Profile, Research, Stock Buzz) but it must be injected and it has not performed well in clinical trials.
Two older drugs are available but flu viruses have quickly developed resistance to them, although some experts believe they may be useful in cocktails with newer drugs.
Flu viruses have a high rate of mutation, which allows them to adapt to the treatments devised to tackle them, so experts recommend having a variety of drugs on hand to treat patients.
"A diversified stockpile of antivirals is important as we are coming to understand that our concerns for the past few years about resistance of pandemic influenza viruses to antivirals were justified," said Dr. Anne Moscona of New York-Presbyterian Hospital/Weill Cornell Medical Center. (Editing by Will Dunham)
