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Update: Domestic H5 Outbreak in BirdsInvestigation into initial human exposures to H5-infected birds suggests risk of human infection is low Language:EnglishEspañolRecommend on FacebookTweetJuly 24, 2015 - - A report published in Emerging Infectious Diseases (EID) today sheds light on the human health risk posed by newly detected highly pathogenic avian influenza H5 viruses in birds in the United States. The investigation identified 164 people exposed to domestic H5 viruses in the United States from December 15, 2014, to March 31, 2015. While some of these exposures included contact with infected birds none have resulted in human infection. These findings support CDC’s current assessment that the risk of human infections from these viruses is relatively currently low. Avian influenza A H5 viruses were detected in birds in the United States in December 2014. The human exposures described in the paper are among the first in the United States. While the EID report details early human exposures to these viruses, no human infections having been detected at this time. Of the 164 human exposures described in the EID report, approximately 63% was associated with H5N2 virus, 34% associated with H5N8 virus, and 2% with H5N1 virus.* While the H5N8 viruses detected in the United States are similar to viruses previously found in birds in other countries, the H5N2** and H5N1 viruses detected in U.S. birds are new reassortant viruses, not previously identified in birds.*** Of the three H5 viruses, H5N2 viruses have been most commonly detected in U.S. birds since December 2014. Of the 164 people with exposures, 64 people were exposed to wild birds, 13 were exposed to captive wild birds, 25 were exposed to poultry on backyard farm(s), and 62 were exposed to poultry on commercial farm(s). More than 48 million domestic birds have been affected with H5 bird flu. Human infections with bird flu viruses are rare but have occurred in the past, most notably with H5N1*** and H7N9 viruses in Asia. Both of these viruses have resulted in sporadic human infections and deaths, most often following prolonged close contact with infected birds. The fact that none of the 164 people followed in the Emerging Infectious Diseases paper were infected is reassuring information. The report does note, however, that exposures in the United States are likely to be different from those in Asia and Africa where socio- and economic factors result in more prolonged, close exposures to birds without the use of PPE. While the risk of human infection with these viruses is considered low at this time, CDC still considers it possible that these viruses may cause human infection resulting in severe disease. CDC recommends that people avoid close or prolonged contact with sick or dead infected poultry and their environments, and that personal protective equipment (PPE) be used when contact cannot be avoided. On June 2, 2015, the agency issued a health alert network advisory which summarized CDC recommendations to protect human health in the context of these domestic H5 bird flu outbreaks. Investigation Details For this investigation, CDC, USDA, the US Department of Interior worked with state health and agriculture departments in Arkansas, California, Idaho, Kansas, Minnesota, Missouri, Oregon, South Dakota, Utah, Washington, and Wyoming to gather H5 exposure information from outbreak areas. Laboratory tests were performed on specimens from patients who were exposed to H5 infected birds and later developed acute respiratory infection (ARI). People involved in flock depopulation were considered separately because of their instruction to wear PPE. During the investigation, CDC received detailed information describing the exposures of 60 people which revealed that (44) 73% had exposure to infected birds while not wearing PPE while engaging in activities such as removing dead birds, collecting eggs, cleaning coops, or feeding birds. Five of 164 people developed ARI within 10 days after their last exposure. Four of five people tested negative for influenza by reverse transcriptase-polymerase chain reaction (RT-PCR) and one person had H3N2 seasonal influenza and no evidence of HPAI H5 virus infection. In addition to the 164 exposed people, zero of 29 persons involved in depopulation activities of infected flocks reported ARI within the 10 days of their last contact with infected birds. Human infection with avian influenza may result from direct exposures like touching infected poultry or poultry parts, and butchering infected poultry or via activities (e.g., feeding poultry and/or cleaning poultry barns) which cause people to come into close proximity to infected birds or their environment. For more CDC recommendations, please visit the CDC avian flu website, or call (800)-CDC-INFO [(800) 232-4636]. # # # *The HPAI H5N8 viruses detected in the United States are similar to viruses that were first reported on duck farms in China in 2009-2010. During 2014, similar HPAI H5N8 viruses were found in wild birds and poultry in Korea and Japan. In November 2014, HPAI H5N8 in poultry and wild birds was reported in England, the Netherlands, Germany and Italy. No human cases have been associated with these HPAI H5N8 viruses. **The HPAI H5N2 viruses detected in the United States are similar to HPAI H5N2 viruses first detected in early December 2014 on poultry farms in British Columbia province, Canada. This is a reassortant virus that combines genes from Eurasian H5 viruses and North American N2 viruses. No human cases have been associated with either the North American or the Eurasian lineages of HPAI H5N2 viruses. ***The HPAI H5N1 virus detected in the United States is a reassortant virus with genes from HPAI H5 Asian viruses and low pathogenic North American viruses. It is different from the H5N1 Eurasian virus that has been associated with human illnesses, including severe disease and death. http://www.cdc.gov/flu/news/update-h5-outbreak-birds.htm

Pathogenesis and transmission of novel HPAI H5N2 and H5N8 avian influenza viruses in ferrets and miceJoanna A. Pulit-Penaloza,Xiangjie Sun,Hannah M. Creager,Hui Zeng,Jessica A. Belser,Taronna R. Maines andTerrence M. Tumpey#+Author Affiliations Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333ABSTRACTA novel highly pathogenic avian influenza (HPAI) H5N8 virus, first detected in January 2014 in poultry and wild birds in South Korea, has spread throughout Asia and Europe, and caused outbreaks in Canada and the United States by the end of the year. The spread of H5N8 and the novel reassortant viruses, H5N2 and H5N1 (H5Nx), in domestic poultry across multiple states in the U.S. pose a potential public health risk. To evaluate the potential of cross-species infection, we determined the pathogenesis and transmissibility of two Asian-origin H5Nx viruses in mammalian animal models. The newly isolated H5N2 and H5N8 viruses were able to cause severe disease in mice only at high doses. Both viruses replicated efficiently in the upper and lower respiratory tracts of ferrets; however clinical symptoms were generally mild and there was no evidence of systemic dissemination of virus to multiple organs. Moreover, these influenza H5Nx viruses lacked the ability to transmit between ferrets in a direct contact setting. We further assessed viral replication kinetics of the novel H5Nx viruses in a human bronchial epithelium cell line, Calu-3. Both H5Nx viruses replicated to a level comparable to a human seasonal H1N1 virus, but significantly lower than a virulent Asian-lineage H5N1 HPAI virus. Although the recently isolated H5N2 and H5N8 viruses displayed moderate pathogenicity in mammalian models, their ability to rapidly spread among avian species, reassort, and generate novel strains underscores the need for continued risk assessment in mammals. IMPORTANCE In 2015, highly pathogenic avian influenza (HPAI) H5 viruses have caused outbreaks in domestic poultry in multiple U.S. states. The economic losses incurred with H5N8 and H5N2 subtype virus infection have raised serious concerns for the poultry industry and the general public due to the potential risk of human infection. This recent outbreak underscores the need to better understand the pathogenesis and transmission of these viruses in mammals, which is an essential component of pandemic risk assessment. This study demonstrates that the newly isolated H5N2 and H5N8 viruses lacked the ability to transmit between ferrets and exhibited low to moderate virulence in mammals. In human bronchial epithelial (Calu-3) cells, both H5N8 and H5N2 viruses replicated to a level comparable to a human seasonal virus, but significantly lower than a virulent Asian-lineage H5N1 (A/Thailand/16/2004) virus. The results of this study are important for the evaluation of public health risk. FOOTNOTES ↵#Corresponding Author: Terrence M. Tumpey, Influenza Division, MS G-16, 1600 Clifton Rd. NE, Atlanta, GA 30333, Tel: 404-639-5444, Fax: 404-639-2350, Email: [email protected] © 2015, American Society for Microbiology. All Rights Reserved.http://jvi.asm.org/content/early/2015/07/24/JVI.01438-15.abstract

New CDC Laboratory Study Suggests U.S. H5 Bird Flu Viruses Currently Pose Low Risk to PeopleLanguage:EnglishEspañolRecommend on FacebookTweetA new CDC study describes findings from a series of CDC laboratory experiments designed to improve understanding of the human health risk posed by two H5 bird flu viruses detected in birds in the United States: H5N2 and H5N8. Findings of this study indicate that the H5N2 and H5N8 bird flu viruses detected in the United States were less lethal in mammals and replicated (made copies of themselves during infection) at a lower level than the H5 bird flu viruses from Asia that have caused infections, serious illness and deaths in people. Overall findings suggest that these new U.S. bird flu viruses are unlikely to easily infect or spread between people in their current form and are likely to be associated with mild to moderate illness compared to the more severe illness associated with Asian H5 viruses. These U.S. bird flu viruses would need to undergo additional changes in order to pose a pandemic health risk to people. This study, published today in the Journal of Virology, involved a combination of laboratory tests, some of which included animals and others that involved human lung cells grown in the laboratory via cell culture. CDC often uses such tests to infer how newly detected flu viruses can impact human health. These studies are part of a routine public health risk assessment process that CDC undertakes whenever a new virus with pandemic potential is identified. Experiments conducted in this study include the following: tests in mice to determine the severity of disease associated with these viruses, tests in ferrets to determine characteristics of how these viruses spread between mammals and within the body, and tests using cell culture to measure the ability of these viruses to grow in human airway/lung cells (specifically human airway epithelial Calu-3 cells) in a laboratory setting. Results in mice showed that mice infected with these viruses did not experience severe disease unless given very high doses of the virus. Virus was detectable in the lungs of mice, though, which is a characteristic that can be associated with more serious illness. However, compared to Asian H5 viruses, these U.S. H5 bird flu viruses demonstrated less severe, more moderate disease characteristics. Health researchers consider mice to be a reliable model for how disease associated with H5 bird flu viruses develops and progresses in mammals. Transmission experiments involving ferrets showed that these U.S. H5 bird flu viruses did not spread between flu naïve ferrets (i.e., ferrets that had never been exposed to flu viruses previously) placed in the same cage as infected ferrets. This indicates that the virus is unlikely to spread efficiently among people, if they were to become infected by close contact with H5N2- or H5N8-infected poultry. Also, illness in the infected ferrets was generally mild, and the viruses did not spread systemically to multiple organs, which is a characteristic associated with more severe disease. These results are consistent with previous studies of H5N8 bird flu viruses in South Korea, which also showed low to moderate virulence in mammals. Ferrets are considered an excellent model for studying flu transmission and they also exhibit signs of disease that are similar to people infected with the flu. Researchers also evaluated the ability of these bird flu viruses to replicate in human lung cells in laboratory experiments involving cell culture. The ability of a virus to infect human lung and airway cells is a trait that can be associated with more severe illness. These tests showed that H5N2 and H5N8 viruses replicated in human lung and airway cells at significantly lower levels compared to the Asian H5N1 viruses that have caused human deaths in Asia and elsewhere. While replication did occur, it was at a level comparable to human seasonal H1N1 flu virus. Outbreaks in birds of H5N2, H5N8 and a new H5N1 bird flu virus were detected in the United States first in late 2014. Both of the bird flu viruses involved in this study were detected in Washington State: the H5N8 bird flu virus was obtained from an infected gyrfalcon and the H5N2 virus was obtained from a northern pintail duck. Most of the U.S. poultry outbreaks reported this year have been associated with the H5N2 virus, resulting in the loss of nearly 50 million chickens and turkeys on over 200 farms since the virus was first identified in December 2014. No human infections with these viruses have been detected at this time. These findings reaffirm CDC’s current assessment that these viruses pose a low risk to the general public. CDC will continue to closely monitor and assess the risk of these viruses to human health as part of its routine pandemic preparedness responsibilities and activities. This study is available for online viewing via the Journal of Virology. The latest information and guidance related to H5 bird flu viruses detected in the United States is available from the CDC H5 Viruses in the United States website. http://www.cdc.gov/flu/news/bird-viruses-risk.htm

http://www.aphis.usda.gov/animal_health/animal_dis_spec/poultry/downloads/ai_conference.pdf

http://www.aphis.usda.gov/animal_health/animal_dis_spec/poultry/downloads/hpai_fall_workshop.pdf

Dear journalists, Please find the link to the audio recording file of the press briefing held today at 12.00 by the WHO Assistant-Director-General Dr Marie - Paule Kieny. The subject is the results from an interim analysis of the Guinea Phase III Ebola vaccine efficacy trial. The link is below: http://terrance.who.int/mediacentre/presser/WHO-RUSH_Ebola_vaccine_results_presser_KIENYm_31JUL2015.mp3 Best regards, WHO Media Team

Dear journalists, Please find the link to the transcript of the press briefing held today at 11.00 by the WHO Director-General and the UN Secretary General’s Special Envoy on Ebola on WHO reform for emergencies with health consequences. http://www.who.int/mediacentre/multimedia/vpc-31-july-2015.pdf?ua=1 Best regards, WHO Media Team

http://www.who.int/mediacentre/multimedia/vpc-31-july-2015.pdf?ua=1

News Release WHO/ 37 31 July 2015 World on the Verge of an Effective Ebola Vaccine Geneva, 31 July 2015 – Results from an interim analysis of the Guinea Phase III efficacy vaccine trial show that VSV-EBOV (Merck, Sharp & Dohme) is highly effective against Ebola. The independent body of international experts - the Data and Safety Monitoring Board – that conducted the review, advised that the trial should continue. Preliminary results from analyses of these interim data are published today in the British journal The Lancet. “This is an extremely promising development,” said Dr Margaret Chan, Director-General of the World Health Organization. “The credit goes to the Guinean Government, the people living in the communities and our partners in this project. An effective vaccine will be another very important tool for both current and future Ebola outbreaks.” While the vaccine up to now shows 100% efficacy in individuals, more conclusive evidence is needed on its capacity to protect populations through what is called “herd immunity”. To that end, the Guinean national regulatory authority and ethics review committee have approved continuation of the trial. “This is Guinea’s gift to West Africa and the world,” said Dr. Sakoba Keita, Guinea’s national coordinator for the Ebola response. “The thousands of volunteers from Conakry and other areas of Lower Guinea, but also the many Guinean doctors, data managers and community mobilisers have contributed to finding a line of defence against a terrible disease.” “The “ring” vaccination method adopted for the vaccine trial is based on the smallpox eradication strategy,” said John-Arne Røttingen, Director of the Division of Infectious Disease Control at the Norwegian Institute of Public Health and Chair of the Study Steering Group. “The premise is that by vaccinating all people who have come into contact with an infected person you create a protective “ring” and stop the virus from spreading further. This strategy has helped us to follow the dispersed epidemic in Guinea, and will provide a way to continue this as a public health intervention in trial mode.” The Guinea vaccination trial began in affected communities on 23 March 2015 to evaluate the efficacy, effectiveness and safety of a single dose of the vaccine VSV-EBOV by using a ring vaccination strategy. To date, over 4 000 close contacts of almost 100 Ebola patients, including family members, neighbours, and co-workers, have voluntarily participated in the trial. The trial stopped randomisation on 26 July to allow for all people at risk to receive the vaccine immediately, and to minimize the time necessary to gather more conclusive evidence needed for eventual licensure of the product. Until now, 50% of the rings were vaccinated three weeks after the identification of an infected patient to provide a term of comparison with rings that were vaccinated immediately. This now stops. In addition, the trial will now include 13 to 17-year-old and possibly 6 to 12-year-old children on the basis of new evidence of the vaccine’s safety. “In parallel with the ring vaccination we are also conducting a trial of the same vaccine on frontline workers,” said Bertrand Draguez, Medical Director at Médecins sans Frontières. “These people have worked tirelessly and put their lives at risk every day to take care of sick people. If the vaccine is effective, then we are already protecting them from the virus. With such high efficacy, all affected countries should immediately start and multiply ring vaccinations to break chains of transmission and vaccinate all frontline workers to protect them. ” The trial is being implemented by the Guinean authorities, WHO, Médecins sans Frontières (MSF) and the Norwegian Institute of Public Health, with support from a broad partnership of international and national organizations. “This is a remarkable result which shows the power of equitable international partnerships and flexibility,” said Jeremy Farrar, Director of the Wellcome Trust, one of the funders of the trial. “This partnership also shows that such critical work is possible in the midst of a terrible epidemic. It should change how the world responds to such emerging infectious disease threats. We, and all our partners, remain fully committed to giving the world a safe and effective vaccine. ” “This record-breaking work marks a turning point in the history of health R&D,” said Assistant Director-General Marie-Paule Kieny, who leads the Ebola Research and Development effort at WHO. “We now know that the urgency of saving lives can accelerate R&D. We will harness this positive experience to develop a global R&D preparedness framework so that if another major disease outbreak ever happens again, for any disease, the world can act quickly and efficiently to develop and use medical tools and prevent a large-scale tragedy.” Note to editors: The vaccine: VSV-EBOV was developed by the Public Health Agency of Canada. The vaccine was licensed to NewLink Genetics, and on November 24, 2014, Merck & Co., Inc and NewLink Genetics Corp. entered into an exclusive worldwide licensing agreement wherein Merck assumed responsibility to research, develop, manufacture, and distribute the investigational vaccine. Financial support was provided by the Canadian and US Governments, among others. A ring vaccination protocol was chosen for the trial, where some of the rings are vaccinated shortly after a case is detected, and other rings are vaccinated after a delay of three weeks. This is an alternative to using a placebo by providing a randomized control group for comparison but at the same time ensures that all contacts are vaccinated within the trial. The trial design was developed by a group of experts from Canada, France, Guinea, Norway, Switzerland, United Kingdom, United States, and WHO. The group included Professor Donald A. Henderson of John Hopkins University, who led the WHO smallpox eradication effort by using the ring vaccination strategy. The partners: The Guinea Ebola vaccine trial is the coordinated effort of many international agencies. WHO is the regulatory sponsor of the study, which is implemented by the Ministry of Health of Guinea, WHO, Médecins sans Frontières (MSF), EPICENTRE and the Norwegian Institute of Public Health. The trial is funded by WHO, with support from the Wellcome Trust, United Kingdom, the Norwegian Ministry of Foreign Affairs to the Norwegian Institute of Public Health through the Research Council of Norway, the Canadian Government through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre and Department of Foreign Affairs, Trade and Development and MSF. The trial team includes experts from The University of Bern, the University of Florida, the London School of Hygiene and Tropical Medicine, Public Health England, the European Mobile Laboratories among others. Media contacts: Daniela Bagozzi Tel: 41 22 791 1990 ; Mob: +41 79 6037281Email: [email protected] Margaret Harris Tel:+ 41 22 7911646; Mob: +41 79 370 0238; Email: [email protected] Gregory Härtl WHO Spokesperson Tel: +41227914458; Mob: +41792036715; Email: [email protected] More information can be found at: http://www.who.int/csr/disease/ebola/en/

Between 16 and 25 July 2015, the National IHR Focal Point for the Kingdom of Saudi Arabia notified WHO of 8 additional cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, including 1 death. Contact tracing of household and healthcare contacts is ongoing for these cases. View the full article

Case Count: Detected U.S. Human Infections with H3N2v by State since August 2011Language:EnglishEspañolRecommend on FacebookTweetTable 1. Case Count: Detected U.S. Human Infections with H3N2v by State since August 2011States Reporting H3N2v CasesCases in 2011Cases in 2012Cases in 2013Cases in 2014Cases in 2015Hawaii 1 Illinois 41 Indiana 213814 Iowa 311 Maine 2 Maryland 12 Michigan 62 Minnesota 5 1Ohio 10712 Pennsylvania 311 Utah 1* West Virginia 23 Wisconsin 20 1 Total 123091931* Case in Utah occurred in April 2012. This chart indicates the number of CDC-reported infections with H3N2v variant influenza A viruses since August 2011 and is current as of July 24, 2015. This case count will be updated each Friday as new cases are reported. NOTE: The state totals reported by CDC may not always be consistent with those reported by state health departments. If there is a discrepancy between these two counts, data from the state health departments should be used as the most accurate number. Table 2. H3N2v Hospitalizations and Deaths Since July 2012*H3N2v Hospitalizations and Deaths Since July 2012Cases in 2012Cases in 2013Cases in 2014Cases in 2015Hospitalizations 16111Deaths 1000* As reported by states to CDC. This chart indicates the number of CDC-reported infections with H3N2v variant influenza A viruses since July 2012 and is current as of July 24, 2015. This case count will be not be updated again until new cases are reported. See Reported Infections with Variant Influenza Viruses in the United States since 2005 for a complete list of human infections with all variant viruses since 2005. http://www.cdc.gov/flu/swineflu/h3n2v-case-count.htm

http://www.oie.int/wahis_2/public\..\temp\reports/en_fup_0000018187_20150722_123232.pdf

Highly pathogenic avian influenza, China (People's Rep. of) Information received on 22/07/2015 from Dr Zhang Zhongqui, Director General , China Animal Disease Control Centre, Veterinary Bureau, Ministry of Agriculture, Beijing, China (People's Rep. of)SummaryReport typeFollow-up report No. 6Date of start of the event12/09/2014Date of confirmation of the event15/09/2014Report date22/07/2015Date submitted to OIE22/07/2015Reason for notificationReoccurrence of a listed diseaseDate of previous occurrence01/05/2014Manifestation of diseaseClinical diseaseCausal agentHighly pathogenic avian influenza virusSerotypeH5N1Nature of diagnosisClinical, Laboratory (basic), Laboratory (advanced)This event pertains toa defined zone within the countryRelated reportsImmediate notification (24/10/2014) Follow-up report No. 1 (09/01/2015) Follow-up report No. 2 (16/01/2015) Follow-up report No. 3 (01/04/2015) Follow-up report No. 4 (19/06/2015) Follow-up report No. 5 (17/07/2015) Follow-up report No. 6 (22/07/2015)New outbreaks (2)Outbreak 1Galongcuo bird island, Anduo, Naqu, TIBETDate of start of the outbreak11/05/2015Outbreak statusContinuing (or date resolved not provided)Epidemiological unitNot applicableAffected animalsSpeciesSusceptibleCasesDeathsDestroyedSlaughteredBar-headed Goose:Anser indicus(Anatidae) 41500Affected populationThere were 415 wild birds dead, including brown-headed gulls and bar-headed geese.Outbreak 2Shuangheer wetland, Kezuohouqi, Tongliao, INNER MONGOLIADate of start of the outbreak11/05/2015Outbreak statusContinuing (or date resolved not provided)Epidemiological unitNatural parkAffected animalsSpeciesSusceptibleCasesDeathsDestroyedSlaughteredBlack-necked Grebe:Podiceps nigricollis(Podicipedidae) 30000Summary of outbreaksTotal outbreaks: 2Total animals affectedSpeciesSusceptibleCasesDeathsDestroyedSlaughteredBar-headed Goose:Anser indicus(Anatidae) **41500Black-necked Grebe:Podiceps nigricollis(Podicipedidae) **30000Outbreak statisticsSpeciesApparent morbidity rateApparent mortality rateApparent case fatality rateProportion susceptible animals lost*Bar-headed Goose:Anser indicus(Anatidae)********Black-necked Grebe:Podiceps nigricollis(Podicipedidae)*********Removed from the susceptible population through death, destruction and/or slaughter**Not calculated because of missing informationEpidemiologySource of the outbreak(s) or origin of infectionUnknown or inconclusive Control measuresMeasures appliedVaccination prohibitedNo treatment of affected animalsMeasures to be appliedNo other measuresDiagnostic test resultsLaboratory name and typeSpeciesTestTest dateResultHarbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (OIE’s Reference Laboratory)Bar-headed Goosereverse transcription - polymerase chain reaction (RT-PCR)29/05/2015PositiveHarbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (OIE’s Reference Laboratory)Bar-headed Goosevirus isolation29/05/2015PositiveHarbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (OIE’s Reference Laboratory)Black-necked Grebereverse transcription - polymerase chain reaction (RT-PCR)29/05/2015PositiveHarbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (OIE’s Reference Laboratory)Black-necked Grebevirus isolation29/05/2015PositiveFuture ReportingThe event is continuing. Weekly follow-up reports will be submitted.Map of outbreak locations http://www.oie.int/wahis_2/public/wahid.php/Reviewreport/Review?reportid=18187

Inner Mongolia, Tibet Death H5N1 bird flu virus detected in wild birdsDate: 2015-05-29 16:53Source: 　　Recently, the Inner Mongolia Tongliao Kezuohouqi doublet Seoul wetland wild birds, Tibet Nagqu Amdo wrong Karma Long Bird Island wild birds of death. The investigation, since mid-May, Tongliao Kezuohouqi doublet Seoul wetlands eared grebe of death, as of May 14, 300 died. Since mid-May, Tibet Nagqu Amdo wrong Karma Long Lake Bird Island and bar-headed goose, brown-headed gulls and other wild birds of death, as of May 25, 415 died. May 29, dead wild birds diseased sample from the National Avian Influenza Reference Laboratory, both of censorship were detected highly pathogenic avian influenza virus subtype H5N1. 　　Currently, the two veterinary departments have jointly forestry sector in accordance with the relevant contingency plans and technical specification requirements, earnestly emergency work to strengthen disinfection and source and monitoring the investigation; local poultry found no abnormalities. http://www.syj.moa.gov.cn/dwyqdt/yqxx/201505/t20150529_4624257.htm

China has reported a H5N1 dieoff of 415 Brown-Headed Gulls and Bar-Headed Geese in Tibet and 300 Black-necked Grebe that occurred in May 2015.

http://www.oie.int/wahis_2/public\..\temp\reports/en_fup_0000018187_20150722_123232.pdf

Highly pathogenic avian influenza, China (People's Rep. of) Information received on 20/07/2015 from Dr Zhang Zhongqui, Director General , China Animal Disease Control Centre, Veterinary Bureau, Ministry of Agriculture, Beijing, China (People's Rep. of)SummaryReport typeFollow-up report No. 5Date of start of the event12/09/2014Date of confirmation of the event15/09/2014Report date17/07/2015Date submitted to OIE20/07/2015Reason for notificationReoccurrence of a listed diseaseDate of previous occurrence01/05/2014Manifestation of diseaseClinical diseaseCausal agentHighly pathogenic avian influenza virusSerotypeH5N1Nature of diagnosisClinical, Laboratory (basic), Laboratory (advanced)This event pertains toa defined zone within the countryRelated reportsImmediate notification (24/10/2014) Follow-up report No. 1 (09/01/2015) Follow-up report No. 2 (16/01/2015) Follow-up report No. 3 (01/04/2015) Follow-up report No. 4 (19/06/2015) Follow-up report No. 5 (17/07/2015) Follow-up report No. 6 (22/07/2015)New outbreaks (1)Outbreak 1Village, Gonghe City, Hainan state, QINGHAIDate of start of the outbreak09/07/2015Outbreak statusContinuing (or date resolved not provided)Epidemiological unitNot applicableAffected animalsSpeciesSusceptibleCasesDeathsDestroyedSlaughteredGreat Black-headed Gull:Larus ichthyaetus(Laridae) 2361236100Summary of outbreaksTotal outbreaks: 1Total animals affectedSpeciesSusceptibleCasesDeathsDestroyedSlaughteredGreat Black-headed Gull:Larus ichthyaetus(Laridae) 2361236100Outbreak statisticsSpeciesApparent morbidity rateApparent mortality rateApparent case fatality rateProportion susceptible animals lost*Great Black-headed Gull:Larus ichthyaetus(Laridae)****100.00%***Removed from the susceptible population through death, destruction and/or slaughter**Not calculated because of missing informationEpidemiologySource of the outbreak(s) or origin of infectionUnknown or inconclusiveContact with wild species Control measuresMeasures appliedControl of wildlife reservoirsMovement control inside the countryDisinfection / DisinfestationDipping / SprayingNo vaccinationNo treatment of affected animalsMeasures to be appliedNo other measuresDiagnostic test resultsLaboratory name and typeSpeciesTestTest dateResultHarbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (OIE’s Reference Laboratory)Great Black-headed Gullreverse transcription - polymerase chain reaction (RT-PCR)17/07/2015PositiveHarbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (OIE’s Reference Laboratory)Great Black-headed Gullvirus isolation17/07/2015PositiveFuture ReportingThe event is continuing. Weekly follow-up reports will be submitted.Map of outbreak locations http://www.oie.int/wahis_2/public/wahid.php/Reviewreport/Review?reportid=18151

Death Qinghai H5N1 bird flu virus detected in wild birdsDate: 2015-07-17 14:00Source: 　　Since early July, the stone is Hai Hainan prefecture, Qinghai County Republican township of death to the public village Pallas's Gull, as of July 15, 2361 death. July 17, the National Avian Influenza Reference Laboratory detection of highly pathogenic avian influenza virus subtype H5N1 deaths expected from the disease sample Pallas's Gull submission of Qinghai Province. 　　At present, Qinghai veterinary departments have jointly forestry sector in accordance with the emergency plan and control technical specifications, really good job in emergency work. The investigation found no local poultry anomalies. http://www.syj.moa.gov.cn/dwyqdt/yqxx/201507/t20150717_4751170.htm

China has reported a H5N1 dieoff of 2361 Great Black-headed Gull's at Qinghai Lake.

http://wwwnc.cdc.gov/eid/article/21/12/15-0809-techapp2.xlsx

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Volume 21, Number 12—December 2015LetterGenetic Characterization of Highly Pathogenic Avian Influenza A(H5N6) Virus, Guangdong, ChinaChris Ka Pun Mok1, Wen Da Guan1, Xiao Qing Liu1, Mart Matthias Lamers1, Xiao Bo Li, Ming Wang, Tami Jing Shu Zhang, Qing Ling Zhang, Zheng Tu Li, Ji Cheng Huang, Jin Yan Lin, Yong Hui Zhang, Ping Zhao, Horace Hok Yeung Lee, Ling Chen, Yi Min Li, Joseph Sriyal Malik Peiris, Rong Chang Chen, Nan Shan Zhong, and Zi Feng Yang Author affiliations: The University of Hong Kong,HKU–Pasteur Research Pole, Hong Kong, China (C.K.P Mok, M.M. Lamers, T.J.S. Zhang, H.H.Y. Lee, J.S.M. Peiris); State Key Laboratory of Respiratory Disease, Guangzhou, China (W.D. Guan, X.Q. Liu, Q.L. Zhang, Z.T. Li, L. Chen, Y.M. Li, R.C. Chen, N.S. Zhong, Z.F. Yang); Guangdong Inspection and Quarantine Technology Center, Guangzhou, (X.B. Li, J.C. Huang); Guangdong Center for Disease Control and Prevention, Guangzhou, (J.Y. Lin, Y.H. Zhang); Guangzhou Center for Disease Control and Prevention, Guangzhou, (M. Wang); Guangzhou Clifford Hospital, Guangzhou, (P. Zhao)Main Article Figure Figure. Phylogenetic trees of A/Guangzhou/39715/2014 based on the A) hemagglutinin (HA) and B) neuraminidase (NA) genes, China. Maximum-likelihood trees were constructed by using the the general time reversible + gamma distribution + invariant sites (GTR+Γ+I) model in MEGA 6.06 (http://www.megasoftware.net). Bootstrap values were calculated on 1,000 replicates; only values >60% are shown. A/Guangzhou/39715/2014 and A/Sichuan/26221/2014 are indicated by a circle and a square, respectively. Vertical lines denote H5 subtype virus clades. Scale bars indicate nucleotide substitutions per site. Full HA and NA trees are provided in the Technical Appendix Main Article 1These authors contributed equally to this article. The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above. http://wwwnc.cdc.gov/eid/article/21/12/15-0809-f1

Volume 21, Number 12—December 2015LetterGenetic Characterization of Highly Pathogenic Avian Influenza A(H5N6) Virus, Guangdong, ChinaOn This PageLetterSuggested CitationFiguresFigureTechnical AppendiciesTechnical Appendix 1Technical Appendix 2DownloadsRIS[TXT - 2 KB]Suggested citation for this article To the Editor: Since the first detection of the influenza A(H5N1) virus in geese in China during 1996 (http://www.cdc.gov/flu/avianflu/h5n1-virus.htm), H5 subtype viruses have continued to reassort and evolve, giving rise to multiple virus clades and gene constellations. Recently, clade 2.3.4.4 viruses have shown a predilection for genetic reassortment, giving rise to H5N2, H5N5, H5N6, and H5N8 virus subtypes, and have become globally widespread, causing infections in wild birds or poultry elsewhere in Asia, and in Europe and North America (1–3). The H5N6 subtype viruses have circulated in China since 2013 and have been mainly identified in ducks or chickens in the southern (Jiangxi, Guangdong) or western (Sichuan) areas (4,5). Two lineages of H5N6 viruses with distant genetic background were found among the H5N6 viruses isolated in China (5). In China, there have been 3 cases of H5N6 virus infection among humans, causing 2 deaths. We recently reported the clinical characteristics and progression of a patient infected by the H5N6 virus in Guangzhou City, China, who was the second reported case-patient infected with this subtype (6). After having contact with poultry, he began to manifest an influenza-like illness on December 3, 2014, and progressed to a primary viral pneumonia. The H5N6 virus A/Guangzhou/39715/2014 (GenBank accession nos. KP765785–KP765792) was isolated from a throat swab specimen collected on day 8 of his illness by inoculation into 9–11-day-old, specific pathogen-free embryonated chicken eggs. He recovered from his infection and was discharged from the hospital on day 58. Multiple sequence alignments showed that the hemagglutinin (HA) and neuraminidase (NA) genes of A/Guangzhou/39715/2014 shared the highest nucleotide identity with A/chicken/Dongguan/2690/2013 (H5N6) (99.4% and 98.3%, respectively) (Technical Appendix[PDF - 2.20 MB - 9 pages] 1). All internal genes were also closely related to A/chicken/Dongguan/2690/2013 (H5N6), ranging from 98.5% nucleotide identity for the polymerase acidic (PA) gene and 100.0% for the matrix (M) gene. The genome segments were also 98.2%–99.7% identical to A/duck/Guangdong/GD012014 and 98.3%–99.4% identical to A/chicken/Laos/LPQ001/2014, which caused outbreaks in domestic ducks and poultry, respectively, indicating that these viruses have the same genotype. Figure. Phylogenetic trees of A/Guangzhou/39715/2014 based on the A) hemagglutinin (HA) and B) neuraminidase (NA) genes, China. Maximum-likelihood trees were constructed by using the the general time reversible + gamma distribution +... HA gene phylogeny confirmed that this virus belonged to clade 2.3.4.4 (Technical Appendix[PDF - 2.20 MB - 9 pages] 1, Figure 4). Notably, the HA genes of the H5N1, H5N2, and H5N8 viruses that were recently detected in wild birds in North America also belong to this clade, indicating that viruses from this clade are becoming globally widespread. More specifically, this isolate clustered within a sublineage that includes H5N6 isolates from poultry from Guangdong and Jiangxi provinces, China, and from Laos (5,7). The A/Sichuan/26221/2014 (H5N6) virus that recently caused a fatal human infection in Sichuan Province, China is also within clade 2.3.4.4, but clusters in a distinct sub-lineage (Figure, panel A). The HA cleavage site of both human isolates contained multiple basic amino acids, suggesting that that they are highly pathogenic avian influenza viruses. Amino acid substitutions E190D, Q226L, or G228S (H3 numbering) in the HA gene that are known to enhance binding to mammalian receptors were not found. The NA gene phylogeny showed that A/Guangzhou/39715/2014 is likely originated from group II lineage influenza A(H6N6) viruses that circulate among domestic ducks in China (8) (Figure, panel B). An 11-aa deletion at the residue 59–69 position of the NA protein was identified in the isolate of this study, in the other H5N6 viruses of the same cluster, and in an H4N6 virus isolate from a duck in Shanghai, China. This deletion was monophyletic and likely originated from A/swine/Guangdong/K6/2010 (H6N6)–like viruses (Figure, panel B). However, it was not observed in other 2.3.4.4 viruses, such as A/Sichuan/26221/2014. No mutations associated with oseltamivir or amantadine resistance was found in NA or M2 genes. The internal genes of the current H5N6 isolate were similar to 2.3.2.1b H5N1 subtype viruses found in domestic ducks from south-central and eastern China (5,7–10 [Technical Appendix[PDF - 2.20 MB - 9 pages] 1]). The 6 internal genes are 97%–99% homologous to another isolate from a human, A/Sichuan/26221/2014, suggesting that the internal genes of the viruses may reassort from a common origin. The phylogenetic clustering observed for the HA gene was also conserved for the internal genes. In contrast with all avian viruses within this clade, the current human isolate contains the mammalian adaptation mutation PB2-E627K, and A/Sichuan/26221/2014 has acquired PB2-D701N, suggesting a rapid acquisition of mammalian adaptation changes that likely arose after human infection. There is still limited information on human disease caused by the emerging H5 lineage. Our genetic analysis suggests that the H5N6 virus isolated from the patient is originated from the avian host. Although the genetic background of H5N6 virus isolated from the third case in Yunnan Province, China, on January 2015 is still not known, the isolates from the human cases of H5N6 infection reported to date show distant genetic diversity, indicating that viruses from both clusters may pose a threat to humans. This rapidly evolving and globally spreading virus lineage thus provides a threat to global public health. Chris Ka Pun Mok1, Wen Da Guan1, Xiao Qing Liu1, Mart Matthias Lamers1, Xiao Bo Li, Ming Wang, Tami Jing Shu Zhang, Qing Ling Zhang, Zheng Tu Li, Ji Cheng Huang, Jin Yan Lin, Yong Hui Zhang, Ping Zhao, Horace Hok Yeung Lee, Ling Chen, Yi Min Li, Joseph Sriyal Malik Peiris, Rong Chang Chen, Nan Shan Zhong, and Zi Feng Yang Author affiliations: The University of Hong Kong,HKU–Pasteur Research Pole, Hong Kong, China (C.K.P Mok, M.M. Lamers, T.J.S. Zhang, H.H.Y. Lee, J.S.M. Peiris); State Key Laboratory of Respiratory Disease, Guangzhou, China (W.D. Guan, X.Q. Liu, Q.L. Zhang, Z.T. Li, L. Chen, Y.M. Li, R.C. Chen, N.S. Zhong, Z.F. Yang); Guangdong Inspection and Quarantine Technology Center, Guangzhou, (X.B. Li, J.C. Huang); Guangdong Center for Disease Control and Prevention, Guangzhou, (J.Y. Lin, Y.H. Zhang); Guangzhou Center for Disease Control and Prevention, Guangzhou, (M. Wang); Guangzhou Clifford Hospital, Guangzhou, (P. Zhao) AcknowledgmentsWe thank the authors and originating and submitting laboratories of the sequences in the EpiFlu Database from Global Initiative on Sharing Avian Influenza Data, on which this research is based. (Technical Appendix 2). This study was supported by Municipal Science and Technology Bureau Foundation of Guangzhou (2014Y2-00031), National Science and Technology Major Project of the Ministry of Science and Technology of China (2014ZX10004006), Science research project of the Guangdong Province (2013B020224006), the Area of Excellence Scheme of the Hong Kong University Grants Committee (AoE/M-12/06) of the Government of Hong Kong Special Administrative Region, China and Contract HHSN272201400006C from the National Institute of Allergy and Infectious Disease, National Institutes of Health, USA. ReferencesWorld Health Organization. Antigenic and genetic characteristics of zoonotic influenza viruses and development of candidate vaccine viruses for pandemic preparedness [cited 2015 Feb 27]. http://www.who.int/influenza/vaccines/virus/201502_zoonotic_vaccinevirusupdate.pdf?ua=1European Food Safety Authority. Highly pathogenic avian influenza A subtype H5N8. EFSA Journal. 2014;12:3941–72.Centers for Disease Control and Prevention. Outbreaks of avian influenza A (H5N2), (H5N8), and (H5N1) among birds—-United States, December 2014–January 2015. MMWR Morb Mortal Wkly Rep. 2015;64:111 .PubMedShen H, Wu B, Chen Y, Bi Y, Xie Q, Influenza A. H5N6) virus reassortant, southern China, 2014. Emerg Infect Dis. 2015;21:1261–2. DOIPubMedBi Y, Mei K, Shi W, Liu D, Yu X, Gao Z, Two novel reassortants of avian influenza A(H5N6) virus in China. J Gen Virol. 2015;96:975–81 .DOIPubMedYang ZF, Mok CKP, Peiris JSM, Zhong NS. Human disease caused by novel reassortant highly pathogenic avian influenza A H5N6 virus: A case report. N Engl J Med. 2015. In press.Wang G, Deng G, Shi J, Luo W, Zhang G, Zhang Q, H6 influenza viruses pose a potential threat to human health. J Virol. 2014;88:3953–64.DOIPubMedWong FY, Phommachanh P, Kalpravidh W, Chanthavisouk C, Gilbert J, Bingham J, Reassortant highly pathogenic influenza A(H5N6) virus in Laos.Emerg Infect Dis. 2015;21:511–6. DOIPubMedHai-bo W, Chao-tan G, Ru-feng L, Li-hua X, En-kang W, Jin-biao Y, Characterization of a highly pathogenic H5N1 avian influenza virus isolated from ducks in eastern China in 2011. Arch Virol. 2012;157:1131–6. DOIPubMedDeng G, Tan D, Shi J, Cui P, Jiang Y, Liu L, Complex reassortment of multiple subtypes of avian influenza viruses in domestic ducks at the Dongting Lake region of China. J Virol. 2013;87:9452–62. DOIPubMedFigureFigure. Phylogenetic trees of A/Guangzhou/39715/2014 based on the A) hemagglutinin (HA) and B) neuraminidase (NA) genes, China. Maximum-likelihood trees were constructed by using the the general time reversible + gamma distribution...Technical AppendicesTechnical Appendix 1. Full phylogenetic trees of polymerase basic 2 (PB2) (Technical Appendix Figure 1), PB1 (Technical Appendix Figure 2), polymerase acidic (PA) (Technical Appendix... 2.20 MBTechnical Appendix 2. Authors and originating and submitting laboratories of the sequences from the Global Initiative on Sharing Avian Influenza Data EpiFlu Database, on which the current research is based. 63 KB Suggested citation for this article: Mok CPK, Guan WD, Liu XQ, Lamers MM, Li XB, Wang M, et al. Genetic characterization of highly pathogenic avian influenza A(H5N6) virus, Guangdong, China [letter]. Emerg Infect Dis. 2015 Dec [date cited]. http://dx.doi.org/10.3201/eid2112.150809 DOI: 10.3201/eid2112.150809 1These authors contributed equally to this article. http://wwwnc.cdc.gov/eid/article/21/12/15-0809_article

Volume 21, Number 12—December 2015ResearchInfection Risk for Persons Exposed to Highly Pathogenic Avian Influenza A H5 Virus–Infected Birds, United States, December 2014–March 2015Carmen S. Arriola , Deborah I. Nelson, Thomas J. Deliberto, Lenee Blanton, Krista Kniss, Min Z. Levine, Susan C. Trock, Lyn Finelli, Michael A. Jhung, and the H5 Investigation GroupAuthor affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA (C.S. Arriola, L. Blanton, K. Kniss, M.Z. Levine, S.C. Trock, L. Finelli, M.A. Jhung); United States Department of Agriculture, Washington, DC, USA (D.I. Nelson); United States Department of Agriculture, Fort Collins, Colorado, USA (T.J. Deliberto)Main Article TableLocation and characteristics of highly pathogenic avian influenza A H5 virus outbreaks among birds and minimum number of exposed persons, United States, December 15, 2014–March 31, 2015 VariableNo. (%) outbreaks among birds, N = 60No. (%) virus-exposed persons*, N = 164State Arizona1 (2)2 (1)California8 (13)30 (18)Idaho8 (13)16 (10)Kansas2 (3)5 (3)Minnesota3 (5)17 (10)Missouri4 (7)26 (16)Montana1 (2)2 (1)New Mexico1 (2)1 (1)Nevada1 (2)5 (3)Oregon10 (17)20 (12)Utah1 (2)1 (1)Washington19 (32)37 (23)Wyoming1 (2)2 (1)Influenza virus subtype† H5N12 (3)3 (2)H5N237 (59)103 (63)H5N822 (35%)56 (34)H5‡2 (3)2 (1)Outbreak setting Wild38 (63)64 (39)Captive5 (8)13 (8)Backyard farm9 (15)25 (15)Commercial farm8 (13)62 (38)No. birds per outbreak 1–542 (70)71 (43)6–5009 (15)29 (18)>5009 (15)64 (39)*Excludes persons who participated in culling activities. †Three outbreaks involved a combination of influenza virus subtypes: H5N1/H5N2 (n = 1) and H5N2/H5N8 (n = 2). ‡No virus was isolated, but specimens were positive by the H5 (intercellular adhesion gene cluster) PCR assay, which targets the Eurasian H5 clade 2.3.4.4 viruses that were detected in the United States in December 2014. Main Article 1Members of the H5 Investigation Group are listed at the end of this article. The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above. http://wwwnc.cdc.gov/eid/article/21/12/15-0904-t1