EINet Alert ~ Oct 20, 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:
- Global: Cumulative number of human cases of avian influenza A/(H5N1)
- Indonesia: 3 additional fatal human cases of avian influenza H5N1
- USA (Illinois): H6N2, low pathogenic avian influenza in wild birds
- USA (Ohio): Low pathogenic avian influenza suspected in wild birds
- USA: CDC seeks data on nondrug prevention of pandemic flu
- USA: Influenza vaccine delay affects toddlers
- USA: CDC puts flu vaccine supply at 115 million doses
- USA: HHS backs respirator use in caring for pandemic flu patients

1. Updates
- Avian/Pandemic influenza updates

2. Articles
- CDC EID Journal, Volume 12, Number 11—Nov 2006
- Priority setting for pandemic influenza: an analysis of national preparedness plans
- Potential risks associated with the proposed widespread use of Tamiflu
- Baxter says cell-based H5N1 vaccine shows potential in trial
- Study supports concept of 2-stage H5N1 vaccination
- Experimental Vaccine Protects Mice Against Deadly 1918 Flu Virus
- Personal (non-pharmaceutical) protective measures for reducing transmission of influenza – ECDC interim recommendations

3. Notifications
- Business Planning for Pandemic Influenza
- Third International Bird Flu Summit

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

Viet Nam / 3 (3)
Total / 3 (3)

Thailand / 17 (12)
Viet Nam / 29 (20)
Total / 46 (32)

Cambodia / 4 (4)
China / 8 (5)
Indonesia / 17 (11)
Thailand / 5 (2)
Viet Nam / 61 (19)
Total / 95 (41)

Azerbaijan / 8 (5)
Cambodia / 2 (2)
China / 12 (8)
Djibouti / 1 (0)
Egypt / 15 (6)
Indonesia / 53 (43)
Iraq / 3 (2)
Thailand / 3 (3)
Turkey / 12 (4)
Total / 109 (73)

Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 256 (151).
(WHO 10/16/06 http://www.who.int/csr/disease/avianinfluenza/en/ )

Avian influenza age & sex distribution data from WHO/WPRO (as of 10/16/06): http://www.wpro.who.int/sites/csr/data/data_Graphs.htm.
(WHO/WPRO 10/16/06)


Indonesia: 3 additional fatal human cases of avian influenza H5N1
As of 16 Oct 2006, the Ministry of Health in Indonesia has confirmed an additional 3 cases of human infection with the H5N1 avian influenza virus. All 3 cases were fatal. The first newly confirmed case occurred in a 67-year-old woman from West Java Province. She developed symptoms 3 Oct 2006, was hospitalized 7 Oct 2006, and died 15 Oct 2006. Diagnosis was complicated by the presence of chronic diseases. Reportedly she had encephalitis. Chickens reportedly died in her household and neighborhood prior to symptom onset. The second case was an 11-year-old male from South Jakarta, Jakarta Province. He developed symptoms 2 Oct 2006, was hospitalized 5 Oct 2006, and died 14 Oct 2006. His recent history included exposure to dead chickens in his neighborhood. The third case was a 27-year-old female from Central Java Province. She developed symptoms 8 Oct 2006, was hospitalized 12 Oct 2006, and died 13 Oct 2006. The source of her exposure is currently under investigation. Of the 72 cases confirmed to date in Indonesia, 55 have been fatal. The total number of deaths from the highly pathogenic H5N1 virus in Indonesia has surpassed that for Viet Nam, making Indonesia the world's hardest hit country by the virus. West Java has so far recorded the highest number of fatalities. The huge territory, backyard-centered farming and low budget have hampered the country's authorities in their fight against avian influenza.
(Promed 10/14/06, 10/15/06, 10/16/06)


USA (Illinois): H6N2, low pathogenic avian influenza in wild birds
The US Departments of Agriculture and Interior announced final test results, which confirm that a low pathogenic avian influenza (LPAI) virus was found in samples collected Sep 2006 from wild Green-winged Teals in Illinois. LPAI has been detected several times in wild birds in North America and poses no risk to human health. The USDA National Veterinary Services Laboratories confirmed the presence of H6N2 through virus isolation in a pool of 5 samples of the 11 samples collected from wild Green-winged Teals in the Rice Lake Conservation Area of Illinois. Because these rapid screening tests are highly sensitive, it is not uncommon to have positive results for a specific subtype on the initial screen test and yet not be able to isolate a virus of that subtype. During confirmatory testing, H5 and N1 subtypes were not found but instead H6 and N2, confirming that the virus is LPAI. Low pathogenic strains occur naturally in wild birds and typically cause only minor sickness or no noticeable signs of disease in birds. Highly pathogenic strains of avian influenza spread rapidly and are often fatal to poultry. For more information: http://www.avianflu.gov.
(Promed 10/18/06)


USA (Ohio): Low pathogenic avian influenza suspected in wild birds
The U.S. Department of Agriculture (USDA) and Department of the Interior (DOI) announced 15 Oct 2006 a detection of H5 and N1 avian influenza subtypes in samples from apparently healthy wild Northern pintails in Ottawa County, Ohio that were killed by a hunter. Initial tests confirm that these wild bird samples do not contain the highly pathogenic H5N1 strain. Initial test results indicate the presence of low pathogenic avian influenza (LPAI) virus, which poses no threat to human health. The samples were collected 8 Oct 2006 through a partnership between USDA and the Ohio Division of Wildlife.

35 samples were collected directly from the birds and screened for H5 at the Ohio Dept. of Agriculture Animal Disease Diagnostic Laboratory. Of those samples, 2 were sent to USDA's National Veterinary Services Laboratories (NVSL) for confirmatory testing, and 1 screened by NVSL tested positive for both H5 and N1 subtypes. This does not mean these birds are infected with an H5N1 strain. It is possible that there could be 2 separate avian influenza viruses, 1 containing H5 and the other containing N1. Confirmatory testing underway at NVSL will clarify whether one or more strains of the virus are present, the specific subtype, as well as confirm the pathogenicity. Low pathogenic avian influenza commonly occurs in wild birds. There is no known health risk to hunters or hunting dogs from contact with low pathogenic forms of avian influenza virus. Nevertheless, hunters are always encouraged to use common sense sanitation practices, such as hand washing and thorough cooking, when handling or preparing wildlife of any kind.
(Promed 10/15/06)


USA: CDC seeks data on nondrug prevention of pandemic flu
CDC plans to fund 8 studies on whether simple measures such as handwashing, "cough etiquette," and face masks could help limit the extent of the next influenza pandemic. CDC announced it would provide a total of $5.2 million to research institutions, some outside the US, to assess nonpharmaceutical measures for battling pandemic flu. The announcement comes amid a wide-ranging CDC effort to come up with specific guidelines on the use of such prevention steps, according to Dr. Martin Cetron, director of the agency's Division of Global Migration and Quarantine. Nonpharmaceutical measures may serve as a first line of defense in a pandemic, since it could take several months to develop an effective vaccine. But officials said there is little evidence about the effectiveness and potential impact of such steps. Besides handwashing, cough etiquette, and masks, community prevention measures include social distancing steps. Other steps include voluntary isolation of patients and voluntary quarantine of their household contacts.

The studies and their principal investigators are as follows: Effectiveness of Selective Non-Pharmaceutical Interventions in Reducing Influenza-Like Illness Among University Students, Tomas Aragon, University of California, Berkeley; Pittsburgh Influenza Prevention Project, Donald Burke and Sam Stebbins, University of Pittsburgh; Nonpharmaceutical Interventions for Pandemic Influenza, Scott Holmberg, RTI International, Research Triangle Park, North Carolina; A Controlled Trial of Masks and Hand Hygiene for Reducing Influenza Transmission, Gabriel Leung, University of Hong Kong; Reducing Transmission of Influenza by Face Masks, Arnold Monto, University of Michigan, Ann Arbor; Stopping Upper Respiratory Infections and Influenza in the Family: the Stuffy Trial, Elaine Larson, Columbia University, New York; Pandemic Influenza Control at the Border of Island Countries and in Households, Michael Baker, University of Otago, New Zealand; Evaluation of Masks as a Source Control Non-Pharmaceutical Intervention, Donald Milton, University of Massachusetts, Lowell.

Cetron said CDC has had requests from public health agencies and other groups for specific guidelines on community prevention measures. When available, the findings of the studies announced will be used to help refine the guidelines. CDC has also asked the Institute of Medicine to assess community prevention measures by examining mathematical modeling studies and historical evidence. CDC has also engaged Harvard University to gauge public opinion and knowledge on the topic. A group led by Dr. Robert Blendon is polling people about their ability or willingness to cooperate in prevention measures, such as by staying home from work when sick and finding child care if schools close.
(CIDRAP 10/13/06 http://www.cidrap.umn.edu/ )


USA: Influenza vaccine delay affects toddlers
The American Academy of Pediatrics (AAP) said that most of this year's supply of seasonal influenza vaccine for children aged 6 months through 3 years will not reach pediatricians until at least Nov. Sanofi Pasteur announced that distribution of its Fluzone injectable vaccine—the only flu vaccine licensed for this age-group—would be about 3 weeks later than last year. About a third of the projected 2006 supply of Fluzone has already been sent to healthcare providers, Sanofi said. "Some healthcare providers may not have their full allotment of vaccine until Nov or later, depending upon when and from which manufacturer they ordered," the company said. CDC said last month it expected that about 75 million doses of vaccine, or three fourths of this year's supply, would be distributed by the end of Oct. AAP is urging pediatricians to notify parents about the delay and encourage them to bring children in for vaccinations later in the year when the vaccine is available. In Jun, federal health officials recommended that toddlers aged 2 through 4 years be immunized against influenza each year, adding millions of people to the groups included in flu vaccination recommendations. CDC recommends that children aged 6 months to 9 years who have never received a flu shot should receive 2 doses of vaccine. Those who receive an injectable vaccine should have a booster 1 month or longer after the initial dose, before the onset of the flu season.
(CIDRAP 10/17/06 http://www.cidrap.umn.edu/ )


USA: CDC puts flu vaccine supply at 115 million doses
CDC increased its estimate of the flu vaccine supply for this season but said many healthcare providers don't have their full supply yet because of distribution issues. Jeanne Santoli, deputy director of CDC's immunization services division, said about 115 million doses of flu vaccine will be available this season, which is 15 million more than the agency's Sep projection. She said 40 million doses were distributed by the end of the second week of Oct, and that 75 million doses would be distributed by the end of the month. CDC's revised estimate follows the Food and Drug Administration's (FDA's) Oct 5 approval of another flu vaccine, ID Biomedical's FluLaval.

CDC has received some complaints from heathcare providers who have received only partial shipments of the vaccine they ordered. Also, the American Academy of Pediatrics said most doses of the only flu vaccine approved for use in children aged 6 months to 3 years, Sanofi's Pasteur's Fluzone, won't be available until at least Nov. Because flu vaccine sales and distribution are handled by private companies, CDC can't control the flow of the product to customers. Vaccine distributors take a phased approach to product delivery, so that all customers receive some of their doses early in the season and can begin immunizing high-risk patients and their household contacts, Santoli said. CDC is NOT recommending that high-risk people be immunized first this year. Santoli said the delay of Fluzone should not impair the benefits of vaccination for young children, and she advised parents to continue seeking the vaccine from their children's' healthcare providers.
(CIDRAP 10/18/06 http://www.cidrap.umn.edu/


USA: HHS backs respirator use in caring for pandemic flu patients
The US Department of Health and Human Services (HHS) has issued new guidance calling for stronger respiratory protection for healthcare workers in the event of an influenza pandemic. A new interim guidance document says the use of N-95 respirators is "prudent" for medical workers providing any direct care for patients ill with confirmed or suspected pandemic flu and is recommended in caring for those with pneumonia. It also says respirator use is prudent for support workers in direct contact with patients. In contrast, HHS's pandemic influenza plan issued last Nov recommends that healthcare workers wear simple surgical masks, designed to block large respiratory droplets, for routine care of pandemic flu patients. The new document also advises healthcare facilities to expect and plan for shortages of N-95 respirators and similar protective equipment in the event of a pandemic.

The new recommendation reflects increased concern about the possibility of airborne transmission of flu viruses, though the document says CDC has found no new scientific evidence on the question. The new advice comes less than a month after a Canadian expert asserted in a CDC journal that the US, Canadian, and British plans for pandemic flu didn't give strong enough advice on respiratory protection for healthcare workers. The new guidance states, "As stated in the plan, the proportional contribution and clinical importance of the possible modes of transmission of influenza (i.e., droplet, airborne, and contact) remains unclear and may depend on the strain of virus ultimately responsible for a pandemic."

But because of the need for "practical clarification," CDC decided to review the evidence again and issue recommendations "to provide a science-based framework to facilitate planning for surgical mask and respirator use" during a pandemic. The report recommends that healthcare workers caring for pandemic flu patients use respirators rated at N-95 or higher during activities likely to generate infectious aerosols, such as intubation, nebulizer treatment, bronchoscopy, and resuscitation. A respirator should be used when providing any kind of direct care for a confirmed or suspected pandemic flu patient who has pneumonia, because such patients may produce unusual amounts of infectious particles when they cough. Further, the guidance says, "Use of N-95 respirators for other direct care activities involving patients with confirmed or suspected pandemic influenza is also prudent. . ."

The new guidance also warns hospital officials to anticipate shortages of respirators. Planners should take care to save enough respirators for use during high-risk procedures, without depriving workers who need them for other activities, it says. It also says managers should take steps to minimize the number of personnel exposed to pandemic flu patients. "If supplies of N-95 (or higher) respirators are not available, surgical masks can provide benefits against large droplet exposure, and should be worn for all health care activities for patients with confirmed or suspected pandemic influenza," the guidance states.

“Interim Guidance on Planning for the Use of Surgical Masks and Respirators in Health Care Settings during an Influenza Pandemic” can be viewed from pandemicflu.gov.
(CIDRAP 10/18/06 http://www.cidrap.umn.edu/ )


1. Updates
Avian/Pandemic influenza updates
- WHO: http://www.who.int/csr/disease/avian_influenza/en/index.html.
- UN FAO: http://www.fao.org/ag/againfo/subjects/en/health/diseases-cards/special_avian.html. Read “EMPRES WATCH: Evolution of Highly Pathogenic Avian Influenza type H5N1 in Europe: review of disease ecology, trends and prospects of spread in autumn-winter 2006” (11pgs, pdf).
- OIE: http://www.oie.int/eng/en_index.htm. Basic information about the upcomeing conference (20-22 Mar 2007), “Vaccination, a tool for the control of avian influenza” is available.
- US CDC: http://www.cdc.gov/flu/avian/index.htm
- The US government’s web site for pandemic/avian flu: http://www.pandemicflu.gov/. You can now select a US map that will take you to a page with links to state pandemic planning information, state pandemic Web site information, and local state contacts. Also available is the new “Interim Guidance on Planning for the Use of Surgical Masks and Respirators in Health Care Settings during an Influenza Pandemic.”
- Health Canada: information on pandemic influenza: http://www.hc-sc.gc.ca/dc-ma/avia/index_e.html. Information on avian influenza: http://www.hc-sc.gc.ca/dc-ma/avia/index_e.html.
- CIDRAP: http://www.cidrap.umn.edu/. Frequently updated news and scholarly articles.
- PAHO: http://www.paho.org/English/AD/DPC/CD/influenza.htm.
- American Veterinary Medical Association: http://www.avma.org/public_health/influenza/default.asp. New updates--Avian influenza backgrounder; USDA, DOI expand wild bird monitoring for avian influenza.
- US Geological Survey, National Wildlife Health Center Avian Influenza Information: http://www.nwhc.usgs.gov/disease_information/avian_influenza/index.jsp. Very frequent news reports.


2. Articles
CDC EID Journal, Volume 12, Number 11—Nov 2006
CDC Emerging Infectious Diseases Journal, Volume 12, Number 11—Nov 2006 issue is now available at: http://www.cdc.gov/ncidod/EID/index.htm. Influenza-related articles include: 1) Anatidae Migration in the Western Palearctic and Spread of Highly Pathogenic Avian Influenza H5N1 Virus. M. Gilbert et al. 2) Susceptibility of North American Ducks and Gulls to H5N1 Highly Pathogenic Avian Influenza Viruses. J.D. Brown et al. 3) Targeted Social Distancing Design for Pandemic Influenza. R.J. Glass et al. 4) Knowledge, Attitudes, and Practices of Avian Influenza, Poultry Workers, Italy. R. Abbate et al. 5) Avian Influenza H5N1 Screening of Intensive Care Unit Patients with Community-acquired Pneumonia. A. Apisarnthanarak et al. 6). Food Markets with Live Birds as Source of Avian Influenza. M. Wang et al. 7) Fatal Avian Influenza A H5N1 in a Dog. T. Songserm et al. 8) Avian Influenza and US TV News. B.G. Southwell et al. 9) Influenza-related Death Rates for Pregnant Women. P. Mortimer. 10) OIE/FAO International Scientific Conference on Avian Influenza. N. Marano.


Priority setting for pandemic influenza: an analysis of national preparedness plans
Lori Uscher-Pines et al. Oct 2006 PLoS Med (Vol 3, Issue 10), published online 17 Oct 2006. (references removed).
“. . .Prioritization of scarce pharmaceutical resources (e.g., vaccines and antiviral medications) that could ultimately delay the spread of a pandemic or lower overall incidence is of particular importance to planning at the national level. Because of costs and manufacturing limitations, these critical resources are likely to be scarce and will require evidence-based rationing. . .Because estimates of global demand for these resources depend on the priorities of individual countries, priority setting at the national level is the first step toward global preparedness. Until recently, developing countries were unlikely to secure supplies of oseltamivir. Today, generic drug manufacturers in Bangladesh, Algeria, India, and China produce oseltamivir, some for local use as determined in official agreements and some for use in areas without patent protection. It seems that the world is entering a phase in which pharmaceutical interventions will not be limited to the developed world—e.g., by spring of 2006, 65 countries had ordered stocks of oseltamivir. . .Despite the growing availability of pharmaceutical resources, the planning community has yet to conduct a critical analysis of distribution strategies. . .Given the integral role of priority setting in the concept of preparedness and the ethical, political, and public health implications of deciding who receives potentially life-saving interventions, we sought to perform a targeted review of national pandemic influenza plans from developed and developing countries. We aim to describe the global variation in national-level prioritization of vaccines and antiviral medications, and to inform future priority-setting processes. . .”
(CIDRAP http://www.cidrap.umn.edu/ )


Potential risks associated with the proposed widespread use of Tamiflu
Environ Health Perspect, published online Oct 11, 2006. Andrew C. Singer et al.
Abstract: “Background: The threat of pandemic influenza has focused attention and resources on virus surveillance, prevention, and containment. The World Health Organization has strongly recommended the use of the antiviral Tamiflu both to treat and prevent pandemic influenza infection. A major concern for the long-term efficacy of this strategy is to limit the development of Tamiflu-resistant influenza strains. However, in the event of a pandemic, hundreds of millions of courses of Tamiflu, stockpiled globally, will be rapidly deployed. Given its apparent resistance to biodegradation and hydrophilicity, oseltamivir carboxylate (OC), the active antiviral and metabolite of Tamiflu, is predicted to enter receiving riverwater, from sewage treatment works, in its active form. Objective: To determine the likely concentrations of oseltamivir carboxylate released into USA and UK river catchments using hydrological modeling and current assumptions about the course and management of an influenza pandemic. Discussion: We predict that high concentrations of OC (µg/L) capable of inhibiting influenza virus replication (µg/L) would be sustained for periods of several weeks, presenting an increased risk for the generation of antiviral resistance and genetic exchange between influenza viruses in wildfowl. Owing to the apparent recalcitrance of oseltamivir carboxylate in sewage treatment works, widespread use of Tamiflu during an influenza pandemic also poses a potentially significant, uncharacterized, ecotoxicological risk in the affected nation’s waterways. Conclusion: To gauge the hazard presented by Tamiflu use during a pandemic we recommend: (1) direct measurement of Tamiflu persistence, biodegradation and transformation in the environment; (2) further modeling of likely drug concentrations in the catchments of countries where humans and waterfowl come into frequent close contact, and where significant Tamiflu deployment is envisaged; and (3) further characterization of the risks to generating Tamiflu-resistant viruses in oseltamivir carboxylate-exposed wildfowl.”
(CIDRAP http://www.cidrap.umn.edu/ )


Baxter says cell-based H5N1 vaccine shows potential in trial
Low doses of a cell-based avian flu vaccine triggered a good immune response to the H5N1 avian influenza virus, according to preliminary results of a clinical trial by Baxter International of USA, maker of the vaccine. The vaccine induced an immune response not only against the targeted H5N1 strain, but against other strains as well, according to Baxter. "This is the first clinical demonstration that a candidate H5N1 vaccine can induce antibodies that neutralize widely divergent strains of H5N1," said Hartmut Ehrlich, vice president for global research and development. He added that the data "suggest that the vaccine may provide wider protection for a larger number of people before and during a pandemic."

The vaccine was produced using Baxter's vero cell–based technology and dead whole viruses of wild-type H5N1 avian influenza strain A/Vietnam/1203/2004. Cell-based vaccines are grown in mammalian cells instead of chicken eggs and in theory could help meet "surge capacity" needs because the cells can be frozen for stockpiling. The method also can shave about a month off the production time for flu vaccines, which is normally about 6 months. The cell-based vaccine was administered to 270 healthy adults aged 18 to 45 in Austria and Singapore. Groups of 44 to 48 volunteers received either 3.75, 7.5, 15, or 30 micrograms (mcg) of the vaccine with an aluminum oxide adjuvant. 2 other groups of 45 each received 7.5 or 15 mcg of vaccine without an adjuvant. All volunteers were vaccinated on the first day of the trial and again 21 days later. 3 weeks after the second injection, testing of serum samples showed that 15 of 23 (65%) volunteers in the 3.75-mcg group had a strong antibody response to the vaccine virus. In comparison, 15 in 20 (75%) of the adjuvanted 7.5-mcg group and 22 of 27 (82%) of the nonadjuvanted 7.5-mcg group showed a strong antibody response. The vaccine also showed evidence of cross-protection against other H5N1 strains. Microneutralization testing for antibody response to a 1997 Hong Kong strain showed a 71% (12 of 17) rate of response in the 3.75-mcg group, compared with an 81% (13 of 16) and a 96% (21 of 22) response in the adjuvanted and nonadjuvanted 7.5-mcg groups, respectively. For a 2005 H5N1 strain from Indonesia, the rates of antibody response were 35% (6 of 17), 63% (10 of 16), and 68% (15 of 22), respectively.

The rate of adverse events demonstrated the apparent safety of the vaccine. After 2 injections, 3% of patients (6 of 201) had fever, 6.0% (12 of 201) experienced malaise, and 3.5% (7 of 201) reported shivering, the company said. Baxter said it plans to begin phase III trials of the vaccine early next year.
(CIDRAP 10/17/06 http://www.cidrap.umn.edu/ )


Study supports concept of 2-stage H5N1 vaccination
The immune system may respond better to a vaccine for a new strain of H5N1 avian influenza if it is prepared in advance with a vaccine based on an existing H5N1 strain. In a study, 37 people who had received an H5N1 vaccine in 1998 were recently given another H5N1 vaccine based on a 2004 strain. They had a much stronger immune response than did another group who received only the newer vaccine, according to the National Institute of Allergy and Infectious Diseases (NIAID). "These preliminary findings need to be confirmed in larger studies, but they offer the intriguing possibility that pre-pandemic priming with existing H5N1 vaccines may boost the immune response to a different H5N1 vaccine tailor-made years later to thwart an emerging pandemic," NIAID Director Dr. Anthony S. Fauci said.

When a pandemic flu strain emerges, it will probably take several months to develop a vaccine to match it, and more than 1 dose will probably be necessary to generate protective immunity, the NIAID said. But providing 2 doses would be logistically difficult, so researchers have been looking for other strategies. One proposed option is to vaccinate people in advance with a related vaccine in the hope that only 1 dose of the pandemic vaccine would be necessary.

After the first human cases of H5N1 illness occurred in Hong Kong in 1997, the NIAID funded the production of an experimental vaccine based on the Hong Kong virus and tested it in a clinical trial at the University of Rochester in 1998. The researchers found 37 people from that trial who were willing to take part in the new study. Participants in the earlier trial had received 2 doses of the vaccine. This year, the 37 volunteers were vaccinated with one 90-microgram (mcg) dose of an H5N1 vaccine based on a strain that circulated in Vietnam in 2004. The vaccine is made by Sanofi Pasteur and is the one the US government is currently stockpiling in the face of the pandemic threat. (That vaccine has shown only modest benefits in trials so far, with about half of vaccinees showing a good immune response after two 90-mcg doses, or about a dozen times the dosage used in seasonal flu vaccine.) The previously vaccinated volunteers had a mean antibody titer (measured by hemagglutination inhibition) of 64, with 70% of them achieving a titer of at least 40. These findings were compared with results in some volunteers who received 90 mcg of the Sanofi vaccine in a previous study and had never had H5N1 vaccine before. These volunteers had a mean antibody titer of 27.1 after one dose, and only 29% had a titer of at least 40. If further studies confirm the findings, pandemic response planners might consider giving a "priming" shot to key personnel, such as healthcare workers, said senior author John J. Treanor.

To see the article: Wing-pui Kong et al. Proc Natl Acad Sci. 2006 Oct 16: http://www.pnas.org/cgi/content/abstract/0607564103v1.
(CIDRAP 10/13/06 http://www.cidrap.umn.edu/ )


Experimental Vaccine Protects Mice Against Deadly 1918 Flu Virus
Scientists have developed a vaccine that protects mice against the killer 1918 influenza virus. They also have created a technique for identifying antibodies that neutralize this virus. These findings are important, the researchers say, to understanding and preventing the recurrence of the H1N1 influenza virus that caused the 1918 pandemic and to protecting against virulent flu strains in the future. Research details are available in Proceedings of the National Academy of Sciences. Gary J. Nabel, director of the Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases (NIAID), led the research team in developing the experimental vaccines and conducting the immunological studies in mice. Terrence Tumpey of CDC conducted vaccine studies in mice involving the live, reconstructed 1918 flu virus.

“A key to containing pandemic flu viruses is to understand their vulnerabilities and determine whether they can evade immune recognition,” says Dr. Nabel. Using the genetic sequence information for the 1918 flu virus, Dr. Nabel and his colleagues created plasmids carrying genes for the virus’ hemagglutinin (HA) protein, the surface protein found in all flu viruses that allows the virus to stick to a cell and cause infection. The researchers created 2 types of plasmids: 1 to reflect the HA found in the original 1918 flu virus; the other an altered HA protein designed to attenuate the virus. Mice were then injected with a DNA vaccine containing both types of plasmids to determine whether they would generate immune responses to the 1918 virus. The researchers found significant responses both in terms of production of T-cells as well as the production of neutralizing antibodies.

To determine the vaccine’s protective effects, Dr. Tumpey intranasally exposed a group of mice to live, reconstructed 1918 virus 14 days after they were immunized with the experimental DNA vaccine. All 10 vaccinated mice survived the challenge. To explore how the vaccine protected the animals, the researchers first depleted other mice of T-cells; however, this had no effect on the immunity of the vaccinated mice to the 1918 virus. In contrast, the researchers discovered that transferring antibody-rich immunoglobulin (IgG) from immunized mice to non-immunized mice resulted in antibody levels in the animals at levels only slightly lower than those that were immunized. When the animals were exposed to the reconstructed 1918 flu virus, 8 of 10 mice that received antibodies from the immunized mice survived; none of the 10 mice that received IgG from the unvaccinated control group survived.

“By using an existing pandemic flu strain, this research will provide the basis for design of alternative vaccines against influenza viruses with enhanced virulence,” says Dr. Tumpey. Although the researchers are not discounting the potential role T-cells may have in combating flu viruses, they concluded that in this study, the experimental DNA vaccine protected the mice by stimulating antibodies capable of neutralizing the 1918 flu virus. To evaluate the vaccine’s antibody-inducing capabilities while minimizing exposure of lab personnel to the 1918 flu virus, Dr. Nabel and colleagues created artificial viruses, or pseudoviruses, featuring the HA of the 1918 flu virus but stripped of the ability to cause infection. The pseudoviruses were then incubated with antibody-containing blood samples from the mice immunized with the DNA vaccine and those that were not. The researchers found that the antibodies from the immunized mice neutralized the pseudoviruses while the blood samples from the mice that were not immunized had no effect. This method was also effective in identifying neutralizing antibodies to the H5N1 avian flu virus and could be used to screen for monoclonal antibodies that may be used as an antiviral treatment, according to Dr. Nabel.
(pandemicflu.gov; NIAID 10/17/06 http://www3.niaid.nih.gov/news/newsreleases/2006/1918vax.htm )


Personal (non-pharmaceutical) protective measures for reducing transmission of influenza – ECDC interim recommendations
A Nicoll, (influenza@ecdc.eu.int), ECDC. Eurosurveillance. Volume 11, issue 10. 12 Oct 2006: http://www.eurosurveillance.org/ew/2006/061012.asp#1 (references removed)
“. . .Earlier this year, the European Centre for Disease Prevention and Control (ECDC) was asked by European Union member state authorities to make recommendations on personal (non-phamaceutical) protective measures that could be taken to reduce the risks of transmission of epidemic and pandemic influenza, either to themselves or from themselves if they are infectious. This work is in addition to that on community-based actions and pharmaceutical measures (vaccination and use of antivirals). . .

The personal protective measures which are supported by the ECDC are listed below:
* Regular handwashing (strongly supported)
* Good respiratory hygiene (covering mouth and nose when coughing or sneezing, using tissues and disposing of them appropriately)
* Mask wearing in healthcare settings (by those with symptoms of acute respiratory infections)
* When influenza is circulating, early isolation at home of people feeling unwell and feverish

. . .There is suprisingly little evidence and almost no experimental studies to show whether personal protective measures work. Indeed, the ECDC’s strongest recommendation is that this topic should receive urgent research attention. Like WHO, the ECDC is neutral but permissive on general mask wearing by everyone during the influenza season as there is no firm evidence as to whether or not this has an impact on transmission. Quarantine, which is the separation or restriction of movement or activity of well people who are thought to have been exposed to influenza and may become infectious to others, is not generally recommended by ECDC for influenza patients, because of practical implications and because infections transmitted by pre-symptomatic people are so rare. However, ECDC would support quarantine if it were recommended by local risk assessments, for example when trying to stop spread in a healthcare setting, or if a person known to be exposed to diagnosed influenza, is nearing the end of the incubation period and has planned to embark on a long journey where self-isolation would be impossible. In the latter case, the person probably should be advised not to travel. During a severe pandemic voluntary household quarantine (asking families to isolate themselves) following diagnosis of a case of influenza in the family might be considered.

With some caveats mentioned above, these recommendations would generally apply both to human seasonal influenza and during an influenza pandemic. They are interim and are subject to continuous review. Further questions and answers are available at the ECDC website (http://www.ecdc.eu.int ). Comments on the recommendations, details of pertinent studies that have been published and not covered in the WHO Reviews, and details of experimental studies that are underway or planned are all welcomed and should be sent to influenza@ecdc.eu.int.”
(CIDRAP http://www.cidrap.umn.edu/ )


3. Notifications
Business Planning for Pandemic Influenza
By providing name, job title, organization, email, and country information, you can receive a free copy of CIDRAP's 10-Point Framework for Pandemic Influenza Business Contingency Planning. You will be kept apprised via e-mail of CIDRAP’s most current initiatives and resources relating to business planning for pandemic influenza. Go to: http://www.cidrap.umn.edu/10points/go.do.
(CIDRAP http://www.cidrap.umn.edu/ )


Third International Bird Flu Summit
The Third International Bird Flu Summit will take place in Geneva, Switzerland, 14-15 November 2006. The purpose of the summit is to prepare the World to fight this potentially infectious disease. WHO and FAO officials will speak at the Summit. For more information, visit: http://www.new-fields.com/birdflu3/index.asp.
(Bird Flu bfsummit@bfsummit.com )