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EINet Alert ~ Jan 06, 2006


*****A free service of the APEC Emerging Infections Network*****
APEC EINet News Briefs offers the latest news, journal articles, and notifications for emerging infections affecting the APEC member economies. It was created to foster transparency, communication, and collaboration in emerging infectious diseases among health professionals, international business and commerce leaders, and policy makers in the Asia-Pacific region.
In this edition:
- Turkey: WHO confirms avian influenza infection in 2 dead children; further results from UK pending
- Ukraine (Crimea): New avian influenza outbreak suspected in poultry
- Eurasia: Cumulative number of human cases of avian influenza A/(H5N1)
- Indonesia: New suspected human case of avian influenza
- China (Sichuan): Confirms new bird flu outbreak
- USA/England: US FDA approves new FluMist plant in England

1. Updates
- Influenza

2. Articles
- CDC EID Journal, Volume 12, Number 1-January 2006
- Lack of autopsies hampering fight against avian influenza


Global
Turkey: WHO confirms avian influenza infection in 2 dead children; further results from UK pending
The Ministry of Health in Turkey has confirmed its first 2 cases of human infection with avian influenza caused by the H5 virus subtype. Both cases were fatal. The first case was a 14-year-old boy from the rural district of Dogubayazit, in the eastern province of Agri, which borders the Islamic Republic of Iran and Armenia. He was hospitalized in Van Province 1 Jan 2006 and died the same day. The second case was his 15-year-old sister, also hospitalized 1 Jan 2006. She died 5 Jan 2006. Earlier this week, Turkish authorities had ruled out avian influenza in these cases based on preliminary test results from samples taken from the nose and throat. Subsequent tests of additional patient specimens taken from the lungs produced positive results. Patient samples were sent to a WHO collaborating centre in the UK for further analysis. Turkish health authorities have informed WHO that, since 1 Jan 2006, a total of 11 patients (including the 2 confirmed fatal cases) have been hospitalized in Van Province with symptoms suggesting infection with avian influenza. Most patients are children between the ages of 6 and 15 years and all reside in the Dogubayazit district. 2 of the children are siblings of the 2 confirmed [i.e. suspected, but not yet independently confirmed] cases. Dr. Ahmet Faik Oner, who treated the children, said the youngsters most likely contracted bird flu while playing with dead chickens.

Following a request by the Ministry of Health, an initial team of experts from WHO, the European Centre for Disease Prevention and Control and the European Commission is travelling 5 Jan 2006 to Turkey to collaborate with the authorities in their investigation. Initial information about the confirmed cases suggests that the children acquired their infection following close contact with chickens. Deaths of chickens are known to have occurred in the Dogubayazit district late 2005. Although no poultry outbreak has been officially reported in the district, a confirmed outbreak of H5N1 avian influenza in chickens and ducks was reported 27 Dec 2005 in the adjacent province of Igdir.

National authorities have informed WHO that the Dogubayazit district has been placed under quarantine; no people or animals are allowed to move in or out of the district. Culling operations are currently under way. The 2 Turkish cases mark the first confirmed reports of human infection with avian influenza outside East Asia. The cases in Turkey bring the number of affected countries to 6, from which 144 cases have now been reported. Turkey reported its first outbreak of H5N1 avian influenza in poultry in mid-October 2005. That outbreak, which occurred in the northwestern part of the country, was attributed to contact between domestic poultry and migratory waterfowl. The outbreak in Igdir and other suspected outbreaks in this part of the country are thought to have occurred following introduction of the virus by migratory birds. The region is known to lie along migratory routes.

WHO appears to be accepting the test results carried out in Turkey, despite the earlier ambiguity (Turkey’s health ministry had earlier denied link of 14 year old boy’s death to avian influenza), and prior to receipt of the results of independent testing from the WHO-affiliated laboratory in the UK. These cases should be designated 'suspected' until results of confirmatory testing in the UK are available. WHO, which had been expecting human cases after the virus was detected amongst birds in Turkey and parts of southeast Europe late 2005, said that this did not mean a worldwide flu pandemic had become more likely. Reportedly, a WHO official said that they had no reason yet to raise its global pandemic alert from the current 3 on a 6-point scale. For the WHO to move to level 4, there would need to be evidence of human-to-human transmission, and there was none yet. (Promed 1/4/06, 1/5/06, 1/6/06)

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Ukraine (Crimea): New avian influenza outbreak suspected in poultry
Ukraine suspects a new outbreak of bird flu in the Crimean peninsula, a regional official was quoted as saying 5 Jan 2006. Mykola Kolesnichenko, head of the emergency commission of the Crimean government, reportedly said that poultry were found dead on a farm in Solnechnoe village in Crimea. He said officials suspected bird flu but would wait for laboratory tests for confirmation. Ukraine reported its first outbreak of bird flu in a dozen villages in Crimea, a major stopover point for migratory birds, in late Nov 2005. Tests from laboratories in Russia and Britain showed it was H5N1 strain. Since then more than 62 000 birds have been destroyed in house-to-house checks in about 30 villages across the Crimean peninsula. Officials declared the bird flu outbreak over and lifted the state of emergency late Dec 2005. For an interactive map showing Crimea's affected counties: http://poultrymed.com/files/index.html. (Promed 1/6/06)

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Asia
Eurasia: Cumulative number of human cases of avian influenza A/(H5N1)
Cumulative number of confirmed human cases of avian influenza A/(H5N1), 2005:
Economy / Cases (Deaths)
Indonesia / 16 (11)
Cambodia / 4 (4)
Thailand / 5 (2)
Viet Nam / 61 (19)
China / 7 (3)
Total / 93 (39)

Cumulative number of confirmed human cases of avian influenza A/(H5N1), 2006:
Economy / Cases (Deaths)
Turkey / 2 (2)
Total / 2 (2)

Total number of confirmed human cases of avian influenza A/(H5N1), 26 Dec 2003 to present: 144 (76)
(WHO 1/5/06 http://www.who.int/csr/disease/avian_influenza/country/en/index.html )

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Indonesia: New suspected human case of avian influenza
An Indonesian man suffering symptoms of avian influenza died 2 Jan 2006, as tests on another man suspected of being the country's 12th fatality from the virus showed he was not infected, health officials said. A 39-year-old man died after being treated for a day at Jakarta's Sulianti Saroso hospital for infectious disease, Indonesia's main bird flu treatment center, hospital spokesman Ilham Patu said. Tests were being carried out to determine whether he died of bird flu. If confirmed, the man would be Indonesia's 12th fatality from the H5N1 virus. "The patient is a suspected bird flu case. He had a history of contact with live and dead chickens," Patu said. The patient was from Tangerang in Banten province, a town southwest of Jakarta where there have been bird flu outbreaks.

Meanwhile, Hariyadi Wibisono, a top health ministry official, said test results had shown that a 48-year-old man from Central Java who died late Dec 2005 suffering bird-flu like symptoms was not infected as had been suspected (the man was reportedly admitted to the Tidar General Hospital in the Central Java town of Magelang suffering high fever and respiratory problems, and died after 10 hours of treatment). Indonesia, the world's fourth most populous nation, was accused of covering up initial outbreaks of bird flu. Most victims in the nation have so far hailed from densely populated Jakarta and its surrounds, where many people live in close proximity to poultry, providing ideal conditions for the virus to pass to humans. (Promed 1/1/06, 1/2/06)

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China (Sichuan): Confirms new bird flu outbreak
China confirmed a bird flu outbreak in the southwestern province of Sichuan, a Food and Agriculture Organization [FAO] official said, adding cold weather and Chinese New Year could mean more cases to come. "In wintertime, we really are concerned because the risk is higher. The more the environment is ideal for the virus, the more outbreaks we are expecting," said Noureddin Mona, China representative for the FAO. More than 1800 poultry were found dead 22 Dec 2005 on a farm in Sichuan's Dazhu County, and Agriculture Ministry officials confirmed the birds had H5N1 infection. Since then, 12 900 poultry in the region have been culled. In response to this outbreak, Hong Kong's government said it had stopped processing requests to import live poultry and poultry meat from Sichuan. Officials say the preponderance of small farms, a lack of well-trained local officials and the world's biggest poultry population will make it hard to contain the disease in China. "The problem in China is about 50-60 percent of the poultry is operated on small-scale farms in the backyard, which provides the ideal life for the virus to jump between different species of poultry," Mona said. He also repeated warnings from the Agriculture Ministry that the risk of the virus spreading could be higher during the Chinese Lunar New Year (late Jan for 2006), as meat consumption and the transport of live poultry increases.

According to an official Chinese notification to the OIE dated 3 Jan 2006, the above outbreak occurred in the village Liuyan (Dazhu county, Sichuan province), starting 22 Dec 2005. The positive result (highly pathogenic avian influenza H5) by the National Avian Influenza Reference Laboratory, Harbin Veterinary Research Institute, was obtained 3 Jan 2006. The pathogen was isolated by SPF eggs inoculation, which required 2 passages. An interactive map, showing China's affected provinces, is available at http://poultrymed.com/files/index.html (go to "maps"). (Promed 1/4/06)

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Americas
USA/England: US FDA approves new FluMist plant in England
A new facility built in England to produce MedImmune's intranasal flu vaccine, FluMist, has gained the US Food and Drug Administration's approval, the company announced. The facility in Liverpool will increase the company's production capacity to about 90 million bulk doses per season, MedImmune said. The company's existing bulk production plant, also in Liverpool, can produce up to 18 million to 20 million bulk doses per season, according to MedImmune spokeswoman Clarencia Stephen. MedImmune made about 3 million doses of FluMist, a live-virus vaccine, for the US market for this flu season. The company shipped about 800,000 doses in the third quarter of 2005. Bulk FluMist is made in Liverpool and shipped to Philadelphia (PA, USA), where it is blended and packaged, Stephen said.

Bernardus Machielse, senior vice president for operations, said the new facility "provides the capacity for manufacture of increased supply of FluMist and our investigational, next-generation influenza vaccine, known as CAIV-T (cold adapted influenza vaccine, trivalent). The facility could also be used to produce vaccine year round in the event of an influenza pandemic." The new plant has 10 times the square footage of the existing facility and has larger testing and storage facilities, the company said. MedImmune hopes to start production in the new plant sometime this year, Stephen said. Because FluMist is sold only in the US, the facility is not facing any British regulatory hurdles, she said. Stephen said it was too early to suggest what effect the plant may have on the supply of FluMist in the US.

MedImmune recently announced favorable preliminary results in a phase 3 study of CAIV-T, a new FluMist formulation that can be stored in liquid rather than frozen form. "It provides greater accessibility and added convenience for healthcare providers, because it no longer needs to be stored in a freezer and it can be administered fairly quickly after it's taken out of the refrigerator," Stephen said. FluMist is currently licensed for use only in healthy people between the ages of 5 and 49 years. The aim of the phase 3 study of CAIV-T was to provide the "pivotal data" to seek approval for use of the vaccine in children down to the age of 6 months, the company said. The trial included about 8,500 children between the ages of 6 and 59 months, including children with a history of asthma and wheezing. Compared with an injectable flu vaccine, CAIV-T yielded a significant 55% reduction in illness caused by any flu strain, MedImmune said. Participant who received the injectable vaccine had an 8.6% rate of flu, versus 3.9% for those who received CAIV-T. (CIDRAP 1/3/06 http://www.cidrap.umn.edu/index.html )

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1. Updates
Influenza
Seasonal influenza activity for the Asia Pacific and APEC Economies
WHO’s surveillance information has not been updated since the 22 Dec 2005 report. Please see EINet’s 23 Dec 2005 Alert for further details. (WHO 12/22/05 http://www.who.int/csr/disease/influenza/update/en/ )

USA. During week 52 (Dec 25 - 31, 2005), influenza activity continued to increase in the US. 169 (10.1%) specimens tested by U.S. WHO and National Respiratory and Enteric Virus Surveillance System (NREVSS) collaborating laboratories were positive for influenza. The proportion of patient visits to sentinel providers for influenza-like illness (ILI) was above the national baseline. The proportion of deaths attributed to pneumonia and influenza was below the baseline level. 7 states reported widespread influenza activity; 3 states reported regional influenza activity; 9 states and the District of Columbia reported local influenza activity; 27 states, and New York City reported sporadic influenza activity; and 2 states reported no influenza activity. (CDC 1/6/06 http://www.cdc.gov/flu/weekly/ )

Avian/Pandemic influenza updates
- WHO’s comprehensive information on the avian influenza: http://www.who.int/csr/disease/avian_influenza/en/index.html. WPRO website on avian influenza: http://www.wpro.who.int/health_topics/avian_influenza/overview.htm. “Pandemic flu: communicating the risks”, an interview with Dr. Margaret Chan, Representative of the Director-General for Pandemic Influenza, is available at: http://www.who.int/bulletin/volumes/84/1/interview0106/en/index.html/.

- Latest FAO updates on avian influenza: http://www.fao.org/ag/againfo/subjects/en/health/diseases-cards/special_avian.html. Includes maps documenting the latest avian flu outbreaks and an interactive timeline of the outbreaks.

- OIE updates and documents on avian influenza: http://www.oie.int/eng/en_index.htm.

- CDC website on pandemic influenza: http://www.cdc.gov/flu/pandemic.htm (includes the new Business Pandemic Plan Checklist and the State and Local Pandemic Influenza Planning Checklist). For avian influenza (available in Chinese, Vietnamese, and Spanish): http://www.cdc.gov/flu/avian/. Infection control measures for preventing and controlling flu transmission in long-term care facilities has been updated 23 Dec 2005: http://www.cdc.gov/flu/professionals/infectioncontrol/longtermcare.htm.

- The US government’s official Web site for pandemic flu: http://www.pandemicflu.gov/. “Planning Guide for Individuals and Families” released 6 Jan 2006.

- Influenza information from the US Food and Drug Administration: http://www.fda.gov/oc/opacom/hottopics/flu.html. Q & A on Using PPE During Influenza Outbreaks, Including Bird Flu: http://www.fda.gov/cdrh/emergency/flu_qa.html.

- Latest CIDRAP updates on avian/pandemic influenza: http://www.cidrap.umn.edu/index.html. A comprehensive overview on avian influenza, updated Dec 20, 2005, is available. The article, “H5N1 avian flu viruses: What's in a name?”, clarifies common questions and confusion arising from the nomenclature. A review of avian influenza in 2005 (“YEAR-END REVIEW: Avian flu emerged as high-profile issue in 2005”) can be obtained from: http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/jan0506review.html.

- PAHO’s latest updates on avian influenza: http://www.paho.org/ Includes article “Avian vs. Pandemic Flu: Understanding the Threat”.

- American Public Health Association (APHA) information on Influenza (http://www.apha.org/preparedness/influenza.htm) and Avian Influenza (http://www.apha.org/preparedness/avian.htm).

- The American Veterinary Medical Association information on avian influenza: http://www.avma.org/public_health/influenza/default.asp
(WHO; FAO, OIE; CDC; US FDA; CIDRAP; PAHO; APHA; AVMA)

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2. Articles
CDC EID Journal, Volume 12, Number 1-January 2006
CDC Emerging Infectious Diseases Journal, Volume 12, Number 1-January 2006 issue is now available at: http://www.cdc.gov/ncidod/EID/index.htm. Numerous articles on influenza are on this issue. The following expedited articles is available online: Free-grazing Ducks and Highly Pathogenic Avian Influenza, Thailand, M. Gilbert et al.

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Lack of autopsies hampering fight against avian influenza
An influenza expert has given warning of a dangerous gap in ability to understand and treat avian influenza because of a failure to conduct post-mortem examinations on most of the victims so far. "The big problem, of course, is that the number of people on whom real extensive pathology has been carried out is limited," said Albert Osterhaus, Head of the National Influenza Centre at Erasmus University in Rotterdam. Of 74 people who have died in the Asian outbreak of H5N1 avian influenza, only 4 or 5 full post-mortems have been carried out, all of them in Thailand. "Autopsies are not regularly done," said Osterhaus. The main barriers in the countries that have confirmed human cases--Thailand, Viet Nam, Cambodia, China and Indonesia--are cultural and religious. Islam, for example, prohibits postmortem examinations under most circumstances. Dr. Osterhaus fears that the lack of post-mortem information will slow the search for a vaccine. (The decline in the inclusion of autopsy reports in routine diagnosis is a general trend. The local health authorities in East Asian countries should be given technical and financial support to facilitate autopsy examinations in human cases of avian influenza.) Such data can help scientists choose the best animal species on which to test potential vaccines, for instance.

A study published 3 Jan 2006 in the online journal Public Library of Science (PLOS): Medicine illustrates the point, he says. A joint Canadian-Chinese team pooled data from 32 victims of SARS from the 2003 outbreak. Some pathologists were said to be reluctant to carry out autopsies because of infection risk. However, the team was able to show that the SARS virus was present in the lungs for only about 2 weeks before being eliminated by the immune system. The researchers also found that death was not due to damage caused by the virus in other tissues. However, 25 of the 32 patients died outside the 2-week window, suggesting that the body's inflammatory response to damage in the lungs could ultimately prove fatal. Treatment of patients with anti-viral drugs was, therefore, vital to limit such damage and save lives. This study, “Time Course and Cellular Localization of SARS-CoV Nucleoprotein and RNA in Lungs from Fatal Cases of SARS”, by Nicholls et al., can be found at: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0030027. (Promed 1/4/06)

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 apecein@u.washington.edu