EINet Alert ~ Jan 02, 2009

*****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:

1. Influenza News
- Cumulative number of human cases of avian influenza A/(H5N1)
- Global: Genetics Provide Evidence for the Movement of Avian Influenza Viruses from Asia to North America via Migratory Birds
- China (Shenzhen)/Hong Kong: Baby infected with avian influenza H9N2
- India (Assam): Avian influenza H5N1 continues to spread among poultry
- India (West Bengal): Reports new avian influenza H5N1 outbreak
- South Korea: Low pathogenic avian influenza identified on duck farm
- Viet Nam: Avian influenza H5N1 confirmed in poultry on two farms
- UK: Seasonal influenza on track to be the worst outbreak in eight years

2. Updates

3. Articles
- Safety, Humoral and Cell Mediated Immune Responses to Two Formulations of an Inactivated, Split-Virion Influenza A/H5N1 Vaccine in Children
- Viral RNA polymerase complex promotes optimal growth of 1918 virus in the lower respiratory tract of ferrets
- Oseltamivir-Resistant Influenza Viruses A (H1N1), Norway, 2007–08
- Avian Influenza Virus (H5N1) in Human, Laos

4. Notifications
- Media partnership project Human Faces of Avian Influenza launched in Indonesia
- Grand Challenges in Global Health Initiative request for proposals

1. Influenza News

Cumulative number of human cases of avian influenza A/(H5N1)
Economy / Cases (Deaths)

Bangladesh / 1 (0)
Cambodia/ 1 (0)
China / 3 (3)
Egypt / 8 (4)
Indonesia / 22 (18)
Viet Nam / 5 (5)
Total / 40 (30)

***For data on human cases of avian influenza prior to 2008, go to:

Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 391 (247).
(WHO 12/16/08 http://www.who.int/csr/disease/avian_influenza/en/index.html )

Avian influenza age distribution data from WHO/WPRO:
http://www.wpro.who.int/sites/csr/data/data_Graphs.htm (WHO/WPRO 12/16/08)

WHO's maps showing world's areas affected by H5N1 avian influenza (last updated 12/24/08): http://gamapserver.who.int/mapLibrary/

WHO’s timeline of important H5N1-related events (last updated 8/14/08):


Global: Genetics Provide Evidence for the Movement of Avian Influenza Viruses from Asia to North America via Migratory Birds
Wild migratory birds may be more important carriers of avian influenza viruses from continent to continent than previously thought, according to new scientific research that has important implications for highly pathogenic avian influenza virus surveillance in North America.

As part of a multi-pronged research effort to understand the role of migratory birds in the transfer of avian influenza viruses between Asia and North America, scientists with the U.S. Geological Survey (USGS), in collaboration with the U.S. Fish and Wildlife Service in Alaska and the University of Tokyo, have found genetic evidence for the movement of Asian forms of avian influenza to Alaska by northern pintail ducks. In an article published in October 2008 in Molecular Ecology, USGS scientists observed that nearly half of the low pathogenic avian influenza viruses found in wild northern pintail ducks in Alaska contained at least one (of eight) gene segments that were more closely related to Asian than to North American strains of avian influenza.

It was a highly pathogenic form of the H5N1 avian influenza virus that spread across Asia to Europe and Africa over the past decade, causing the deaths of 245 people and raising concerns of a possible human pandemic. The role of migratory birds in moving the highly pathogenic virus to other geographic areas has been a subject of debate among scientists. Disagreement has focused on how likely it is for H5N1 to disperse among continents via wild birds.

"Although some previous research has led to speculation that intercontinental transfer of avian influenza viruses from Asia to North America via wild birds is rare, this study challenges that," said Chris Franson, a research wildlife biologist with the USGS National Wildlife Health Center and co-author of the study. Franson added that most of the previous studies examined bird species that are not transcontinental migrants or were from mid-latitude locales in North America, regions far removed from sources of Asian strains of avian influenza.

Scientists with the USGS, in collaboration with the U.S. Fish and Wildlife Service, state agencies, and Alaska native communities, obtained samples from more than 1,400 northern pintails from locations throughout Alaska. Samples containing viruses were then analyzed and compared to virus samples taken from other birds in North America and Eastern Asia where northern pintails are known to winter. Researchers chose northern pintails as the focus of the study because they are fairly common in North America and Asia, they are frequently infected by low pathogenic avian influenza, and they are known to migrate between North America and Asia. None of the samples were found to contain completely Asian-origin viruses and none were highly pathogenic.

"This kind of genetic analysis - using the low pathogenic strains of avian influenza virus commonly found in wild birds - can answer questions not only about the migratory movements of wild birds, but the degree of virus exchange that takes place between continents, provided the right species and geographic locations are sampled," said John Pearce, a research wildlife biologist with the USGS Alaska Science Center and co-author of the study. "Furthermore, this research validates our current surveillance sampling process for highly pathogenic avian influenza in Alaska and demonstrates that genetic analysis can be used as an effective tool to further refine surveillance plans across North America, Pearce added.

Implications of the Research
• Migratory bird species, including many waterfowl and shorebirds, that frequently carry low pathogenic avian influenza and migrate between continents may carry Asian strains of the virus along their migratory pathways to North America. • USGS researchers found that nearly half of influenza viruses isolated from northern pintail ducks in Alaska contained at least one of eight virus genes that were more closely related to Asian than North American strains. None of the samples contained completely Asian-origin viruses and none were highly pathogenic forms that have caused deaths of domestic poultry and humans. • The central location of Alaska in relation to Asian and North American migratory flyways may explain the higher frequency of Asian lineages observed in this study in comparison to more southerly locations in North America. Thus, continued surveillance for highly pathogenic viruses via sampling of wild birds in Alaska is warranted.

The website for the USGS northern pintail avian influenza research is http://alaska.usgs.gov/science/biology/avian_influenza/pintail_movements.html.
(USGS 10/27/08)


China (Shenzhen)/Hong Kong: Baby infected with avian influenza H9N2
Health officials in Hong Kong said a 2-month-old girl who lives in mainland China has been hospitalized at a Hong Kong hospital for an H9N2 avian influenza infection, which typically causes mild illness but is considered one of the viruses that could evolve into a pandemic strain. Thomas Tsang, controller for Hong Kong's Centre for Health Protection, said that the girl was in stable condition and is in isolation.

The baby and her family live in Shenzhen, in southern China, but she was hospitalized in Hong Kong after she became sick. "We have had four [H9N2] cases in the past 10 years and they all had mild respiratory symptoms and they all recovered," Tsang stated. He added that the virus is common among chickens and geese in southern China.

Tsang said health officials in China's Guangdong province are investigating how the girl contracted the virus. Hong Kong's last H9N2 case was reported in March 2007, when the virus struck a 9-month-old girl. The same subtype sickened two girls in 1999 and a 5-year-old boy in 2003.

Though the H9N2 strain of avian flu is distinct from the H5N1 subtype, global health experts regard it as one of the other avian influenza viruses that could evolve into a pandemic strain. Researchers have reported that the virus can spread to pigs, in which it could potentially reassort with other influenza viruses that are more likely to infect humans. Serologic studies have suggested that there may be more human H9N2 infections than have been detected and reported.
(CIDRAP 12/30/08)


India (Assam): Avian influenza H5N1 continues to spread among poultry
The Assam government has reported that avian influenza has spread to new areas of the state. Sources in the Animal Husbandry and Veterinary Department said that the bird flu virus was confirmed in about 15 more villages. The health authorities have been asked to cull nearly 70 000 birds in these areas.

A veterinary department official said, "So far, about 150 villages in eight Assam districts were hit by birdflu, and Rapid Response Teams have already slaughtered about 510,000 chickens and ducks since 27 Nov 2008." The latest report added that culling was in progress in the new areas, including Manahkuchi of Hajo, Chayani Barduar block in Kamrup (Rural), Tihu-Barama of Baksa, Chachaligaon Burachowk in Nagaon, Rangamati and Aurpakmoniari Tiniali in Kamrup (Metro).

"We have so far identified 19 epicenters affected by bird flu in Assam. Culling operations in newly affected areas have already begun, while in some places, the drive is almost complete," added the official. The official said the source of the virus was difficult to ascertain as it was air-borne. The Assam government has already banned sale and movement of poultry products from bird flu affected areas.

The bird flu virus was first detected in Kamrup (Rural) district on 27 Nov 2008. Since then, more than 500,000 poultry have been culled by state authorities. Furthermore, the Union government has also established the outbreak of the disease among the poultry of Doloigaon Uzanpara village under Dhaligaon Development Block of Bongaigaon District.
(ProMED 12/31/08)


India (West Bengal): Reports new avian influenza H5N1 outbreak
Health and veterinary workers culled poultry in a densely populated eastern Indian state on 3 January 2009 after a fresh outbreak of H5N1 bird flu, officials said. The latest outbreak of the virus in poultry is the fourth in the state of West Bengal since 2007.

West Bengal officials said they had begun culling about 60,000 poultry after the fourth outbreak was confirmed on Saturday near Siliguri town, bordering Bangladesh. Culling operations in West Bengal to contain the third outbreak had ended just two weeks prior to the latest outbreak. "We have sent 30 teams to kill chickens and ducks in the village where dead birds tested positive," Surendra Gupta, a senior government official, stated.
(Reuters 1/3/09)


South Korea: Low pathogenic avian influenza identified on duck farm
As part of the on-going control measures for avian influenza in the Republic of Korea, surveillance has been conducted since September 2008 on all duck farms. On 29 December 2008, fecal samples collected from the duck farm tested positive to haemagglutination (HA) test. On 31 December 2008, the virus was identified as low pathogenic avian influenza virus subtype H5N2, by HA, inhibition of neuraminidase (NA) and gene sequencing. All ducks on the affected farm were slaughtered on 23 December 2008, but government officials reported the finding to the World Organization for Animal Health (OIE) on 2 January 2009.
(OIE 1/2/09)


Viet Nam: Avian influenza H5N1 confirmed in poultry on two farms
Bird flu has resurfaced in poultry in northern Viet Nam after many months without any cases, killing ducks and chickens at two farms. Animal health officials confirmed on 27 Dec 2008 that the H5N1 virus had killed several birds among a flock of more than 100 ducks in Thai Nguyen city, 80 km north of Hanoi. Officials had also detected the virus in dead chickens at a farm in the same city, and nearly 4200 chickens had been slaughtered to prevent the virus from spreading.

Deputy Health Minister Trinh Quan Huan said earlier in the week of 21 Dec 2008 that there was a very high risk of bird flu returning during the winter and spring of 2008-2009 in northern Viet Nam. The H5N1 strain seems to thrive in low temperatures.

Five Vietnamese have died of bird flu so far in 2008 out of six reported H5N1 infections, and all were found in northern Viet Nam during the first quarter of the year. Viet Nam has had 106 infections since 2003, the second highest number of cases after Indonesia among 15 countries with known human cases.
(ProMED 12/28/08)


UK: Seasonal influenza on track to be the worst outbreak in eight years
Experts are warning that the current outbreaks of flu are expected to intensify in the 2009, as the Australian strain that can be fatal spreads across the UK. The current flu epidemic, which is already on course to be the worst in eight years, will get worse as the infection usually peaks between January and March.

The European Influenza Surveillance Scheme (EISS) says the H3N2 Brisbane 10 flu strain that caused a severe epidemic and killed six children in Australia is spreading, with the UK, Ireland, Bulgaria and Spain experiencing it at "medium intensity." The UK Health Protection Agency and the Royal College of General Practitioners (GPs) have reported a sharp rise in the number of flu-like illnesses at the end of December 2008, with retirees being the worst hit.

The sharp rise left the National Health Service (NHS) struggling to cope over the week of 21 December 2008. Thousands of GPs' offices close over this period, leaving sufferers with nowhere to go for help except accident and emergency wards. But hospitals are already under more pressure than usual because of outbreaks of the winter vomiting bug norovirus. Latest figures show that among those over 65 years of age, 45 in every 100,000 people now have flu, up from just 18 in the week prior to 21 December 2008. Though it is still the 15 to 44 years of age group who are reporting the most cases, at a rate of 80 per 100,000, it is the elderly who are most likely to die from flu.

The 2008 outbreak, blamed on an Australian strain of the virus called Brisbane H3N2, is well on course to be the worst since 1999, when 22,000 people died. However, an outbreak does not officially become an epidemic until the infections rate is higher than 200 people per 100,000. The last time that happened was in 1989.

Professor Steve Field, chairman of the Royal College of GPs, said, "Older age groups are now showing increases, and they have the most serious consequences -- the extra load on the lungs, possible viral pneumonia and the increased risk of contracting a second bacterial infection. The NHS is coping remarkably well in the circumstances, although there are some very desperate problems in the West Midlands. The outbreak is affecting young adults and many of these are health service workers. When added together, there are a lot of problems. The influenza vaccination program has been good in some areas but patchy in others. It is these areas where the NHS will take a big hit."

The Health Protection Agency said: "Although it is too early to predict how much further flu will increase, the agency's advice is to be alert to symptoms. These can include a headache, fever, cough, sore throat, and aching muscles and joints. For the majority of people, flu is an unpleasant, but not life-threatening, illness. But it can be dangerous for certain groups, such as the elderly or those with heart problems, diabetes or asthma and those who are immuno-compromised."
(ProMED 12/31/08)


2. Updates
- UN: http://www.undp.org/mdtf/influenza/overview.shtml UNDP’s web site for information on fund management and administrative services and includes the website of the Central Fund for Influenza Action. This site also includes a list of useful links.
- WHO: http://www.who.int/csr/disease/avian_influenza/en/index.html The (interim) Influenza Virus Tracking System can be accessed at: www.who.int/fluvirus_tracker.
- UN FAO: http://www.fao.org/avianflu/en/index.html. View the latest avian influenza outbreak maps, upcoming events, and key documents on avian influenza.
- OIE: http://www.oie.int/eng/info_ev/en_AI_avianinfluenza.htm. Link to the Communication Portal gives latest facts, updates, timeline, and more.
Epidemiological updates on the avian influenza outbreak in Hong Kong available at http://www.oie.int/wahis/public.php?page=single_report&pop=1&reportid=7609 and the outbreak in India at http://www.oie.int/wahis/public.php?page=single_report&pop=1&reportid=7606.
- US CDC: Visit "Pandemic Influenza Preparedness Tools for Professionals" at:
http://www.cdc.gov/flu/pandemic/preparednesstools.htm. This site contains resources to help hospital administrators and state and local health officials prepare for the next influenza pandemic.
- The US government’s website for pandemic/avian flu: http://www.pandemicflu.gov/. View archived Webcasts on influenza pandemic planning.
- CIDRAP: http://www.cidrap.umn.edu/ Find more than 150 peer-reviewed practices from 25 US states and 37 cities and counties aimed at furthering pandemic preparedness in public health and allied fields.
- PAHO: http://www.paho.org/English/AD/DPC/CD/influenza.htm Link to the Avian Influenza Portal at:
http://influenza.bvsalud.org/php/index.php?lang=en. The Virtual Health Library’s Portal is a developing project for the operation of product networks and information services related to avian influenza.
- US National Wildlife Health Center: http://www.nwhc.usgs.gov/disease_information/avian_influenza/index.jsp. Read about the latest news on H5N1 in wild birds and poultry.


3. Articles
Safety, Humoral and Cell Mediated Immune Responses to Two Formulations of an Inactivated, Split-Virion Influenza A/H5N1 Vaccine in Children
Chotpitayasunondh T et al. PLoS One. 29 December 2008; 3(12). Available at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0004028.


Highly pathogenic influenza A/H5N1 has caused outbreaks in wild birds and poultry in Asia, Africa and Europe. It has also infected people, especially children, causing severe illness and death. Although the virus shows limited ability to transmit between humans, A/H5N1 represents a potential source of the next influenza pandemic. This study assesses the safety and immunogenicity of aluminium hydroxide adjuvanted (Al) and non adjuvanted influenza A/Vietnam/1194/2004 NIBRG-14 (H5N1) vaccine in children.

Methods and Findings
In a Phase II, open, randomised, multicentre trial 180 children aged 6 months to 17 years received two injections, 21 days apart, of vaccine containing either: 30 µg haemagglutinin (HA) with adjuvant (30 µg+Al) or 7.5 µg HA without adjuvant. An additional 60 children aged 6–35 months received two “half dose” injections (ie 15 µg+Al or 3.8 µg). Safety was followed for 21 days after vaccination. Antibody responses were assessed 21 days after each injection and cellular immune responses were explored. Vaccination appeared well tolerated in all age groups. The 30 µg+Al formulation was more immunogenic than 7.5 µg in all age groups: in these two groups 79% and 46% had haemagglutinination inhibition antibody titres ≥32 (1/dil). Among 6–35 month-olds, the full doses were more immunogenic than their half dose equivalents. Vaccination induced a predominantly Th2 response against H5 HA.

This influenza A(H5N1) vaccine was well tolerated and immunogenic in children and infants, with Al adjuvant providing a clear immunogenic advantage. These results demonstrate that an H5N1 Al-adjuvanted vaccine, previously shown to be immunogenic and safe in adults, can also be used in children, the group most at risk for pandemic influenza.


Viral RNA polymerase complex promotes optimal growth of 1918 virus in the lower respiratory tract of ferrets
Watanabe T et al. Proc Natl Acad Sci. 29 December 2008 (early online publish). Available at http://www.pnas.org/content/early/2008/12/29/0806959106.abstract.

The 1918 influenza pandemic was the most devastating outbreak of infectious disease in human history, accounting for about 50 million deaths worldwide. In addition to a significant number of cases of secondary bacterial pneumonia, this highly pathogenic strain of influenza A virus caused fatal primary viral pneumonia. To identify the viral gene(s) chiefly responsible for the high virulence of the 1918 virus, we generated a series of reassortants between the 1918 virus and a contemporary human H1N1 virus (A/Kawasaki/173/2001; K173) using reverse genetics. We then assessed their virulence properties in ferrets, a model closely resembling humans in terms of sensitivity to influenza virus infection and pattern of spread after intranasal inoculation. Substitution of single genes from the 1918 virus in the genetic background of K173 virus did not markedly alter the pattern of infection. That is, the reassortants grew well in nasal turbinates, but only sporadically (if at all) in the trachea and lungs. One exception was the 1918PB1/K173 reassortant, which replicated efficiently in lung tissues as well as the upper respiratory tract. A reassortant virus expressing the 1918 viral RNA polymerase complex (PA, PB1, and PB2) and nucleoprotein showed virulence properties in the upper and lower respiratory tracts of ferrets that closely resembled those of wild-type 1918 virus. Our findings strongly implicate the viral RNA polymerase complex as a major determinant of the pathogenicity of the 1918 pandemic virus. This new insight may aid in identifying virulence factors in future pandemic viruses that could be targeted with antiviral compounds.


Oseltamivir-Resistant Influenza Viruses A (H1N1), Norway, 2007–08
Hauge SH et al. Emerg Infect Dis. February 2009 (early online publication). Available at http://www.cdc.gov/eid/content/15/2/pdfs/08-1031.pdf.

In Norway in January 2008, unprecedented levels of oseltamivir resistance were found in 12/16 influenza viruses A (H1N1) tested. To investigate the epidemiologic and clinical characteristics of these viruses, we used sequence analysis to test all available subtype H1N1 viruses from the 2007–08 season for resistance. Questionnaires from physicians provided information on predisposing diseases, oseltamivir use, symptoms, and complications. Clinical data were obtained for 265 patients. In total, 183 (67.3%) of 272 viruses were oseltamivir resistant. Resistance was not associated with prior use of antiviral drugs. Symptoms and hospitalization rates did not differ for patients infected with a resistant or a susceptible virus. Oseltamivir-resistant influenza viruses A (H1N1) did not show diminished capability to spread in the absence of selective pressure. The ability of these viruses to sustain their fitness and spread among persons should be considered when shaping future strategies for treating and preventing seasonal and pandemic influenza.


Avian Influenza Virus (H5N1) in Human, Laos
Puthavathana P et al. Emerg Infect Dis January 2009; 15(1). Available at http://www.cdc.gov/eid/content/15/1/127.htm.

Letter to the editor
The first avian influenza (H5N1) outbreak in poultry in Laos occurred in 2003 and subsided in March 2004 after massive killing of poultry to contain the disease. Extensive surveillance from July 2005 through January 2006 did not detect any influenza virus subtypes in chicken, ducks, quails, and pigs in live bird markets in the Vientiane, Champasak, and Savannakhet Provinces. Avian influenza virus (H5N1) was reintroduced into Laos in February 2006 but showed a lower incidence. Viruses isolated in this country in 2004 belonged to genotype Z, clade 1, and 2006 isolates belonged to clade 2.3.4.

Avian influenza (H5N1) had not been reported in humans in Laos until February 27, 2007. Our patient was a 15-year-old adolescent girl who lived in a suburb of Vientiane where an outbreak of influenza (H5N1) in poultry had been confirmed on February 7, 2007. Influenza-like symptoms developed in the patient on February 10. She was hospitalized in Vientiane with fever and respiratory symptoms on February 15. On February 17, her parents brought her to a private hospital in Nong Khai Province, Thailand. Oseltamivir was prescribed on February 19. On February 20, she was transferred to the Nong Khai Provincial Hospital because of rapid, progressive, severe pneumonia with acute respiratory distress syndrome. When we suspected avian influenza in this patient, clinical specimens were tested.
(Excerpt with references removed.)


4. Notifications
Media partnership project Human Faces of Avian Influenza launched in Indonesia
Established talents and rising stars from Indonesia's media celebrated the opening this week of an exhibition of work they had produced as part of a competitive media partnership project – Human Faces of Avian Influenza – organized by FAO and the Indonesian Ministry of Agriculture.

Well-known Indonesian novelist/singer Dewi Lestari hosted the event at a packed Galeri Foto Jurnalistik Antara (Antara Gallery) in Jakarta. She was joined by the 13 successful media partners and an enthusiastic crowd of over 200 senior government staff, media professionals, representatives of international organizations, donors, artists and members of the public, for an evening of presentations, music, photographic and audio-visual exhibitions, and film screenings. The exhibition has already been extended beyond its initial three days due to very high popular demand.

Opening the event, Dr. Turni Rusli Sjamsuddin, Director of Veterinary Public Health in the Indonesian Ministry of Agriculture, on behalf of the Director General of Livestock Services, Dr Tjeppy Soedjana, said that “with this program, we expect to be able to develop avian influenza communication by focusing on those people who suffer the biggest losses and highest risks (because this will enable us) to gain greater awareness of the impact of AI in communities; communication allows interaction between disease control measures and livelihood/markets/cultural practices, and increases community participation in response to AI.”

The ‘Human Faces of Avian Influenza’ was launched in July 2008 to award mini-fellowships to media practitioners based in Indonesia in the fields of print, radio, television, video, digital/online media, photography and multi-media. The aim was to mobilize media professionals as catalysts in the communication and advocacy process, include the views and opinions of the communities most affected by or at risk from avian influenza in the communication process, and develop a range of high-quality media materials and outputs to create awareness of and change risky behavior in relation to avian influenza.

The media partnership project was funded by the Canadian International Development Agency (CIDA), with additional resources and support provided by the US Agency for International Development (USAID) and the Australian government's aid programme, AusAID.

For further information on the project, visit the project website at http://mediapartnership.wordpress.com or contact Ester Hutabarat, National PDSR Communication Officer (ester.hutabarat@gmail.com) or Enrico Aditjondro, Media Liaison and Information Officer (aditjondro@gmail.com).
(FAO 12/19/08)


Grand Challenges in Global Health Initiative request for proposals
The McLaughlin-Rotman Centre for Global Health (MRC) and its Ethical, Social and Cultural Program (ESC) for the Grand Challenges in Global Health (GCGH) Initiative are pleased to invite individuals, institutions, organizations and companies from the developing world to submit proposals to carry out projects that will facilitate the implementation and use of technologies in the developing world that arise from the GCGH projects.

The goal of this Request for Proposals (RFP) is to select and commission research on strategies that will facilitate the implementation and appropriate use in the developing world of technologies that arise from the GCGH projects related to diagnostics, modified insect vectors, nutritionally enhanced foods, and vaccine delivery. Visit WWW.MRCGLOBAL.ORG/RFP for further information. The deadline to submit proposals is January 16, 2009.