EINet Alert ~ Aug 15, 2008

*****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
- Global: Cumulative number of human cases of avian influenza A/(H5N1)
- Global: FAO says avian influenza H5N1 situation in birds has improved
- United Kingdom: Britain ranks influenza pandemic among top threats
- Indonesia (Sumatra): Suspected avian influenza H5N1 cases test negative; concern remains

2. Updates

3. Articles
- Emerging Infectious Diseases - Volume 14, Number 8 – August 2008
- Influenza shots may not protect elderly from pneumonia
- Pathogenicity of highly pathogenic avian influenza virus (H5N1) in adult mute swans
- Researchers probe pandemic potential of avian influenza H9N2 virus
- Pandemic management and developing world bioethics: bird flu in West Bengal

4. Notifications
- No Ordinary Flu: Preparedness comic book in multiple languages

1. Influenza News

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

Bangladesh / 1 (0)
China / 3 (3)
Egypt / 7 (3)
Indonesia / 18 (15)
Viet Nam / 5 (5)
Total / 34 (26)

***For data on human cases of avian influenza prior to 2008, go to: http://depts.washington.edu/einet/humanh5n1.html

Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 385 (243).
(WHO 6.19.08 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 6.19.08)

WHO's maps showing world's areas affected by H5N1 avian influenza (last updated 6.19.08): http://gamapserver.who.int/mapLibrary/

WHO’s timeline of important H5N1-related events (last updated 7.14.08): http://www.who.int/csr/disease/avian_influenza/ai_timeline/en/index.html


Global: FAO says avian influenza H5N1 situation in birds has improved
The global H5N1 avian influenza situation in birds improved in the first half of this year, but an H5N1 strain not previously seen in Africa recently cropped up in Nigeria, according to the United Nations Food and Agriculture Organization (FAO). "Considering the number of outbreaks reported worldwide, the global HPAI [highly pathogenic avian influenza] situation can be said to have improved markedly in the first half of 2008," the FAO said in the latest issue of its avian flu bulletin, AIDEnews.

However, four countries where H5N1 is endemic—Egypt, China, Indonesia, and Vietnam—continued to report outbreaks during the 6-month period, and the virus re-emerged in Pakistan and in Hong Kong's live bird markets, FAO noted. In June, 11 H5N1 outbreaks were reported in five countries (China, Egypt, Indonesia, Pakistan, and Vietnam), compared with 65 outbreaks in June 2006 and 55 in June 2007, the FAO said. Europe reported no outbreaks, unlike in June of previous years, and no cases were reported in wild birds. However, Indonesia has not submitted reports on H5N1 events since May, because the new database for the country's Participatory Disease Surveillance system is being modified, according to the report. "Although there has been an improvement in disease awareness, outbreaks/cases of HPAI are still underestimated and underreported in many countries because of limitations in country disease surveillance systems, which may affect considerably the shape of the distribution of outbreaks by region," the FAO said.

In a statement about Nigeria, the FAO said recent avian flu outbreaks in the states of Katsina and Kano involved a strain that has never been reported in Africa before but is similar to strains identified in Italy, Afghanistan, and Iran in 2007. The agency did not identify the strain by clade or subclade. Scott Newman, international wildlife coordinator for the FAO's Animal Health Service, said the discovery is a concern. "It seems to be unlikely that wild birds have carried the strain to Africa, since the last migration of wild birds from Europe and Central Asia to Africa occurred in September 2007 and this year's southerly migration into Africa has not really started yet," Newman said. He said the new strain could have been introduced through international trade or illegal and unreported movement of poultry. A team of FAO experts is working with the Nigerian government on disease surveillance, outbreak investigations, and the establishment of veterinary drug stockpiles, the agency said.

In other developments, the pathogenicity of H5N1 strains circulating in Vietnam seems to be rising, according to another article in AIDEnews. Investigators from the US Department of Agriculture and colleagues from Vietnam's National Centre for Veterinary Diagnosis said the increase in pathogenicity is manifested by more severe respiratory tract infections in ducks and an increase in cloacal virus levels. Jan Slingenbergh of the FAO's Animal Health Service said that despite the increased pathogenicity, avian flu in southern Vietnam is well in check. Slingenbergh said that longitudinal studies carried out by Joerg Henning from the Australian Centre for International Agricultural Research (ACIAR) in four different provinces of the Mekong Delta from May to November 2007 suggest that seroprevalence rates in unvaccinated chickens and ducks were between 5-20 percent but that there were low levels of virus shedding (few PCR-positives) and no HPAI outbreaks. Repeated vaccination in layer ducks appears very effective in protecting them from HPAI: out of 152 outbreaks recorded during the peak season (mid-November 2006 to mid-February 2007) in 66 communes scattered across the Mekong Delta, only one single outbreak involved layer ducks that had been vaccinated twice.

Therefore, commented Slingenbergh, continued vaccination in layer ducks appears to be critical. With ducks the predominant poultry species in the Mekong Delta and with 80 percent of these [being] layer ducks, the FAO expert believes that HPAI in the southern part of Viet Nam is well in check. However, he added, northern Viet Nam requires strengthening with measures other than vaccination, and the cost of vaccination campaigns cannot continue to be entirely supported by public funds only.
(CIDRAP 8/11/08; Promed 8/10/08)


Europe/Near East
United Kingdom: Britain ranks influenza pandemic among top threats
A new report from the British government ranks pandemic influenza very high on the list of major security threats to the United Kingdom. The National Risk Register, prepared by Britain's Cabinet Office, depicts pandemic flu as the biggest threat in terms of potential impact on the country, well above such risks as terrorist attacks, coastal flooding, and major industrial accidents. It says a pandemic could infect as much as half of the British population and kill as many as 750,000. The 52-page report portrays a pandemic as somewhat less likely than terrorist attacks on transport and crowded places but just slightly less likely than severe weather. The report is described as "an assessment of the most significant emergencies which the United Kingdom and its citizens could face over the next five years".

The document is part of Prime Minister Gordon Brown's overhaul of homeland security strategy, according to an Associated Press (AP) report. It said Brown ordered the drafting of a list of threats shortly after he replaced Tony Blair in June 2007, arguing that previously classified assessments should be made public. Noting that 228,000 Britons died in the flu pandemic of 1918-19, the document says that history, scientific evidence, and modeling suggest that up to half the UK population could contract the flu and between 50,000 and 750,000 people could die of it.

"Normal life is likely to face wider social and economic disruption, significant threats to the continuity of essential services, lower production levels, shortages and distribution difficulties," the document states. It says the government has stockpiled enough oseltamivir (Tamiflu) to treat up to 25% of the population. "This should be sufficient to treat all those who fall ill in a pandemic of similar proportions to those that occurred in the 20th century," it states. The government also has "advanced supply agreements" to buy enough doses of pandemic-specific vaccine for the whole population, if needed, but delivery of the first doses would not start until 4 to 6 months after the emergence of the pandemic, according to the report.

The Register is intended to help people improve their own preparedness. It lists further information resources, discusses business continuity planning, and offers suggestions for individual, family, or community-based preparations. Calling itself "a first attempt to inform the public more fully of the types of risks that we face," the report invites readers to provide feedback for consideration in future updates.
(CIDRAP 8/8/08)


Indonesia (Sumatra): Suspected avian influenza H5N1 cases test negative; concern remains
In an online statement, the Indonesian government said 12 villagers from North Sumatra who were hospitalized for suspected avian influenza symptoms had tested negative for the disease, dampening speculation about a possible case cluster. The statement from the health ministry's avian flu committee, known as KOMNAS FBPI, said 12 villagers from Air Batu village tested negative for the H5N1 virus. All were being treated at Kisaran Hospital, except for a 7-year-old girl and an 8-year-old boy who were at Adam Malik Hospital in Medan, the provincial capital, where they were reported to be in stable condition.

The ministry's statement did not mention three deaths from suspicious symptoms that have been mentioned along with accounts of up to 13 sick patients in recent media reports. However, Chandra Syafei, an official from North Sumatra's health office, acknowledged that three people had died and said his office was on "extraordinary occurrence" alert status, according to a Jakarta Post report. He said his office had not received autopsy reports from the health ministry. The suspected cases were identified by provincial and local health officials between Aug 5 and 7, and the patients were given oseltamivir when they were hospitalized, the health ministry's statement said. Also, it said the ministry was conducting surveillance in the area for more patients with suspicious symptoms.

The ministry's message, its first since Jun 19, 2008, said the tests were conducted by its Health Research and Development Center. Official news out of Indonesia about H5N1 developments has been scarce since early June, when Health Minister Siti Fadilah Supari said the country would stop reporting human cases as they occur and instead announce them at longer intervals, perhaps as long as 6 months. Syafei said several health workers, including a team from the World Health Organization (WHO), were in Asahan to investigate the illnesses and monitor developments, according to the Post report. He said animal health officials had destroyed 276 infected birds, and an official from nearby Labuhan Ratu regency said local veterinary workers culled 1,126 birds after hundreds of recent poultry deaths, the Post reported. The health ministry statement said tests conducted by North Sumatra's livestock office on 15 poultry that died suddenly on Jul 28, 2008 were positive for avian influenza. The ministry announced earlier this week that the human toll from avian influenza in Indonesia had risen to 112 following the recent death of a 19-year-old man.
(CIDRAP 8/13/08; Promed 8/10/08)


2. Updates
- UN: http://www.undp.org/mdtf/influenza/overview.shtml UNDP recently launched a new 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 to governments, international agencies, NGOs, and scientific organizations.
- WHO: http://www.who.int/csr/disease/avian_influenza/en/index.html The Influenza Virus Tracking System (interim) is now live and can be accessed by the public at: www.who.int/fluvirus_tracker.
- UN FAO: http://www.fao.org/avianflu/en/index.html. FAO AIDEnews and other documents can also be found here. View the latest cumulative highly pathogenic avian influenza outbreak maps at http://www.fao.org/avianflu/en/maps.html.
- OIE: http://www.oie.int/eng/info_ev/en_AI_avianinfluenza.htm. Link to the Communication Portal gives latest facts, updates, timeline, and more.
- US CDC: http://www.cdc.gov/flu/avian/index.htm. 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 the recent Guidance on Pandemic Vaccination Allocation and Report on Home Health Care during an Influenza Pandemic.
- CIDRAP: http://www.cidrap.umn.edu/ Information on the upcoming “Big 7 Pandemic-Planning Mistakes” Webinar (October 9, 2008)
- PAHO: http://www.paho.org/English/AD/DPC/CD/influenza.htm. See the Situation Report: Influenza A (H1N1) Virus Resistance to Oseltamivir--2008 Influenza Season, Southern Hemisphere. Link to the Avian Influenza Portal at: http://influenza.bvsalud.org/php/level.php?lang=en&component=19&item=1.
- US Geological Survey, National Wildlife Health Center Avian Influenza Information: 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
Emerging Infectious Diseases - Volume 14, Number 8 – August 2008
New August 2008 issue online at: http://www.cdc.gov/ncidod/eid/. Several articles of interest are listed below:
- Sirenda Vong et al. Environmental contamination during influenza A virus (H5N1) outbreaks, Cambodia, 2006. http://www.cdc.gov/eid/content/14/8/1303.htm
- Kirk M et al. Obligations to report outbreaks of foodborne disease under the International Health Regulations (2005). http://www.cdc.gov/eid/content/14/9/pdfs/08-0468.pdf
- Uchida Y et al. Highly pathogenic avian influenza virus (H5N1) isolated from whooper swans, Japan. http://www.cdc.gov/eid/content/14/9/pdfs/08-0655.pdf
- Toby Leslie et al. Knowledge, attitudes, and practices regarding avian influenza (H5N1), Afghanistan. http://www.cdc.gov/eid/content/14/9/pdfs/07-1382.pdf


Influenza shots may not protect elderly from pneumonia
Studies designed to tease out the benefits of seasonal influenza vaccines for elderly people have yielded conflicting results over the past few years, and now new findings suggest that the vaccine's ability to reduce the risk of pneumonia may be less than expected. The researchers, who studied seniors enrolled in a Washington state health maintenance organization (HMO) over three flu seasons, published their findings in the Aug 2, 2008 issue of The Lancet. The lead author is Michael L. Jackson, a postdoctoral fellow at the Group Health Center for Health Studies in Seattle. Experts strongly recommend flu shots for the elderly, because the disease increases the risk of problems such as cardiac events and pneumonia. However, some recent studies have cast doubt on the mortality benefits of flu shots for the elderly, and some experts have said that confounding factors in past studies led to an overestimation of vaccine benefits for this age-group.

The Lancet report describes a population-based case-control study focusing on immunocompetent people aged 65 to 94 years, identified from HMO data from the 2000, 2001, and 2002 flu seasons, when the vaccines closely matched circulating flu strains. The case-group included those who had community-acquired pneumonia between the date each year when the vaccine became available and the end of the flu season. Each case-patient was matched by age and sex with two controls. The authors describe a variety of steps they took to control for underlying heath differences between cases and controls and other factors that might confound assessment of the vaccine's ability to protect elderly people from pneumonia.

For example, the researchers:
- Excluded people who were living in nursing homes or were immunocompromised
- Assessed the presence and severity of various health conditions, such as asthma, chronic lung disease, congestive heart failure, dementia, stroke, alcoholism, and diabetes
- Assessed functional limitations
- Validated pneumonia diagnoses on the basis of two criteria: the presence of a nonchronic parenchymal infiltrate on chest radiograph or the attending physician's conclusion that pneumonia was the most likely diagnosis
- Included people who received outpatient treatment for their pneumonia, not just those who were hospitalized

The authors used a two-step process to reduce confounding. First they looked at the relation between flu vaccination and the risk of pneumonia during "preinfluenza" periods—the time between the first availability of flu shots and the start of the flu season. They found that vaccination was linked with an apparent 40% reduction in pneumonia risk during this interval—an effect that was attributed not to vaccination but to better health among the vaccinees, since flu was not yet present in the community. The investigators then adjusted statistically for the various potential confounding factors (differences in underlying health conditions, medication use, and functional status) until the apparent reduction in pneumonia risk for vaccinated people during the preinfluenza period was eliminated. Next, they adjusted for these confounding factors in an analysis of pneumonia risk during the flu season, when an effect of vaccination was expected.

The authors identified 1,173 patients who had pneumonia and 2,346 controls. Flu vaccination rates were nearly equal in the groups: 77% in the patients and 78% in the controls. The researchers found that vaccination did not significantly reduce the risk of pneumonia in this population. The odds ratio was 0.92 (95% confidence interval [CI], 0.77 to 1.10; P=0.66). For individual seasons, vaccinees were found to have a 6% lower risk of pneumonia in 2000-01, a 2% higher risk in 2001-02, and a 21% lower risk in 2002-03, but none of these differences were significant. Vaccination was found to be even less protective when the analysis was restricted to the 210 pneumonia cases that occurred during the peak of each flu season (a 5-week period with the peak-illness week in the middle). The odds ratio was 1.04 (95% CI, 0.70 to 1.55; P=0.84).

One limitation of the study is that some patients could have received flu vaccines outside the managed-care setting, the report says. However, the controls had higher vaccination rates than those for Washington seniors overall, which would reduce the chance of misclassification. Jackson et al. write that their findings could mean one of two things: that influenza causes only a small proportion of pneumonia in elderly people, or that the vaccine is not very effective in reducing the risk of the influenza infection in the elderly. The two possibilities have different implications for vaccine development and vaccination recommendations, they add. "Differentiation between them will need studies with laboratory-confirmed endpoints, such as pneumonia or serious respiratory outcomes after a confirmed influenza infection."

It is not yet possible to say which of the two possible implications of the study is more accurate, according to two infectious disease experts, Edward Belongia and David Shay, who wrote a commentary accompanying the report. Belongia is a senior epidemiologist at the Marshfield Clinic Research Foundation in Marshfield, Wis., and Shay is a medical officer in the CDC’s influenza division. The commentators praise the authors' efforts to purge sources of bias that may have affected previous observational studies in which vaccination was found to be protective against pneumonia. Belongia and Shay cite three factors that may explain the different results between Jackson's study and the observational studies: adjustments for confounding by differences in patients' health status, the careful validation of pneumonia diagnoses, and the inclusion of both hospitalized and outpatient subjects. More studies are needed to explore the causes of pneumonia in seniors, particularly those who have received flu immunizations, Belongia and Shay write. Also, they said standard methods are needed to assess vaccine efficacy across different seasons and in different populations.

In an Aug 2, 2008 press release from the Group Health Center for Health Studies, Jackson said his findings shouldn't dampen efforts to vaccinate older people against the flu. "Despite our findings, and even though immune responses are known to decline with age, I still want my grandmother to keep getting the flu vaccine," he said. "The flu vaccine is safe. So it seems worth getting, even if it might lower the risk of pneumonia and death only slightly." Some flu experts have called for development of new vaccines that offer more protection for elderly people, and manufacturers are developing adjuvanted vaccines in keeping with that aim, according to previous reports.

Jackson ML, Nelson JC, Weiss NS, et al. Influenza vaccination and risk of community-acquired pneumonia in immunocompetent elderly people: a population-based, nested case-control study. Lancet 2008 Aug 2;372(9636):398-405. http://www.thelancet.com/journals/lancet/article/PIIS0140673608611605/abstract

Belongia EA, Shay DK. Influenza vaccine for community-acquired pneumonia. (Commentary) Lancet 2008 Aug 2;372(9636):352-4
(CIDRAP 8/8/08)


Pathogenicity of highly pathogenic avian influenza virus (H5N1) in adult mute swans
Kalthoff D, Breithaupt A, Teifke JP, Globig A, Harder T, Mettenleiter TC, et al. EID 14(8): 1267-1270] http://www.cdc.gov/eid/content/14/8/1267.htm

Adult, healthy mute swans [Cygnus olor] [were experimentally infected with highly pathogenic avian influenza [HPAI] virus A/Cygnus cygnus/Germany/R65/2006 subtype H5N1. Immunologically naive birds died, whereas animals with preexisting, naturally acquired avian influenza virus-specific antibodies became infected asymptomatically and shed virus. Adult mute swans are highly susceptible, excrete virus, and can be clinically protected by pre exposure immunity.


Researchers probe pandemic potential of avian influenza H9N2 virus
Scientists have warned it's impossible to predict which avian influenza virus will spark the next pandemic, and while most of the attention has been on highly pathogenic H5N1, one research group is reporting new findings that raise concerns about the threat from the low-pathogenic H9N2 virus. The international group of researchers, mainly from the University of Maryland, published their findings in the August issue of PLoS One. They used ferrets, which have sialic acid receptors in their respiratory tracts resembling those in humans, to explore how H9N2 viruses replicate and transmit.

The H9N2 subtype has been found in many avian species in Asia, the Middle East, Europe, and Africa over the past decade, the authors write. The virus can cause mild-to-moderate disease in humans. In March 2007, Hong Kong officials reported that a 9-month-old girl was infected with the strain, the fourth time since 1999 that the virus was found in a child from that city. US officials have worried that H9N2 could evolve into a pandemic strain. In 2004, the National Institute of Allergy and Infectious Diseases (NIAID) contracted with Chiron Corp. (now part of Novartis) to produce a vaccine against the virus. In Sept 2006 researchers reported that the experimental vaccine generated a good immune response in a phase 1 clinical trial. The contract tapped Chiron to produce 40,000 doses of a vaccine containing an inactivated strain of H9N2 developed by the Centers for Disease Control and Prevention.

The PLoS One report says that many H9N2 isolates have acquired human virus–like receptor specificity, preferentially binding alpha 2-6 sialic acid receptors. Some studies have shown that H9N2 viruses extensively evolve and reassort, while others have shown that the viruses have spread to pigs, which could provide a "mixing vessel" with flu viruses that are more likely to infect humans. Also, serologic studies have suggested that there may be more human cases of H9N2 than have been detected and reported so far.

In their study, the searchers first evaluated whether five wild-type H9N2 viruses could infect ferrets and whether infected animals could spread the disease to other ferrets through direct contact and through the air. Lethargy, anorexia, and temperature elevations were noted in some of the ferrets that were inoculated with the virus, and the virus was found in nasal washes from all the inoculated ferrets. Most of the ferrets caged with the inoculated animals showed evidence of viral shedding and had H9 antibodies.

They also investigated whether one of the H9N2 viruses they used could be transmitted by aerosol to ferrets. Though the virus was found in the inoculated and direct-contact ferrets, they found no seroconversion in ferrets that were kept separate but shared the same air as the other animals. "Taken together, these data indicate that although some H9N2 viruses can transmit to direct contacts, they lack successful aerosol transmission," the report says.

Another goal was to determine if an H9N2 avian-human reassortment would enhance transmission of H9N2 strains that contained Leu226. Using reverse genetics, they recovered a reassortant that combined surface protein genes from H9N2 with internal genes from an H3N2 virus. Ferrets that were inoculated with the virus, as well as their direct contacts, had high H9 antibody titers, but the aerosol contacts did not. The authors report that the reassortant virus showed enhanced shedding and transmission, but it lacked the ability to infect aerosol contacts. The reassortant also caused more severe damage in the lungs, replicating in both the upper and lower respiratory tracts, than a wild-type H9N2 virus. The group concluded that H9N2 viruses are poised for further adaptation that could make transmission more efficient among mammals and humans. Though they did not find aerosol transmission, a key feature of a pandemic influenza strain, an abundance of other risk factors, such as the human virus-like specificity in some avian and swine isolates, build a strong case for H9N2 as a potential public health threat , they assert.

Wan H, Sorrell EM, Song H, et al. Replication and transmission of H9N2 influenza viruses in ferrets: evaluation of pandemic potential. PLoS One 2008 Aug;3(8):1-13. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0002923
(CIDRAP 8/14/08)


Pandemic management and developing world bioethics: bird flu in West Bengal
Chhanda Chakraborti. Dev World Bioeth. 2008 Aug 11. [Epub ahead of print] http://www3.interscience.wiley.com/journal/121376101/abstract?CRETRY=1&SRETRY=0

Abstract: This paper examines the case of a recent H5N1virus (avian influenza) outbreak in West Bengal, an eastern state of India, and argues that poorly executed pandemic management may be viewed as a moral lapse. It further argues that pandemic management initiatives are intimately related to the concept of health as a social 'good' and to the moral responsibility of protection from foreseeable social harm from an infectious disease. The initiatives, therefore, have to be guided by special moral obligations towards biorisk reduction, obligations which remain unfulfilled when a public body entrusted with the responsibility fails to manage satisfactorily the prevention and control of the infection. The overall conclusion is that pandemic management has a moral dimension. The gravity of the threat that fatal infectious diseases pose for public health creates special moral obligations for public bodies in pandemic situations. However, the paper views the West Bengal case as a learning opportunity, and considers the lapses cited as challenges that better, more effectively conducted pandemic management can prepare for. It is hoped that this paper will provoke constructive bioethical deliberations, particularly pertinent to the developing world, on how to ensure that the obligations towards health are fulfilled ethically and more effectively.


4. Notifications
No Ordinary Flu: Preparedness comic book in multiple languages
To promote pandemic flu preparedness, Public Health - Seattle & King County has developed a 12-page comic book on pandemic flu. Targeting readers of all ages, this story tells the tale of a family’s experience of the 1918 influenza pandemic. It also explains the threat of pandemic flu today, illustrates what to expect during a pandemic (such as school closures), and offers tips to help households prepare. You can order copies (or download) all 12 language versions of the comic (PDF format) at the above link.
(CIDRAP 7.23.08)