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EINet Alert ~ Oct 06, 2006


*****A free service of the APEC Emerging Infections Network*****
APEC EINet News Briefs offers the latest news, journal articles, and notifications for emerging infections affecting the APEC member economies. It was created to foster transparency, communication, and collaboration in emerging infectious diseases among health professionals, international business and commerce leaders, and policy makers in the Asia-Pacific region.
In this edition:
- Global: Cumulative number of human cases of avian influenza A/(H5N1)
- China (Ningxia Hui): Avian influenza H5N1 outbreak kills 1000 poultry
- China (Inner Mongolia): Avian influenza H5N1 outbreak kills 1000 poultry
- Indonesia (East Java): 69th human case of H5N1 avian influenza infection
- Indonesia: Healthy chickens test positive with H5N1 virus
- Indonesia: Avian influenza H5N1 may infect a quarter of Indonesia's domestic birds
- USA (Illinois): Mild avian influenza virus found in ducks
- USA: Influenza workers seek to dispel vaccination myths
- USA: FDA issues guide to ease production of cell-based vaccines
- USA: FDA approves fifth flu vaccine--FluLaval

1. Articles
- Groups call for pandemic flu vaccine 'master plan'
- Injectable drug seen as potential treatment for influenza, both seasonal and avian
- Airborne influenza viruses threaten health workers, expert says
- Seasonal and Pandemic Influenza: Recommendations for Preparedness in the United States
- Childhood Influenza Vaccination Coverage --- United States, 2004--05 Influenza Season
- Influenza and pneumococcal vaccination coverage among persons aged >65 Years--United States, 2004--2005

2. Notifications
- Avian/Pandemic influenza updates


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

2003
Viet Nam / 3 (3)
Total / 3 (3)

2004
Thailand / 17 (12)
Viet Nam / 29 (20)
Total / 46 (32)

2005
Cambodia / 4 (4)
China / 8 (5)
Indonesia / 17 (11)
Thailand / 5 (2)
Viet Nam / 61 (19)
Total / 95 (41)

2006
Azerbaijan / 8 (5)
Cambodia / 2 (2)
China / 12 (8)
Djibouti / 1 (0)
Egypt / 14 (6)
Indonesia / 50 (40)
Iraq / 3 (2)
Thailand / 3 (3)
Turkey / 12 (4)
Total / 105 (70)

Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 252 (148).
(WHO 10/3/06 http://www.who.int/csr/disease/avianinfluenza/en/ )

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Asia
China (Ningxia Hui): Avian influenza H5N1 outbreak kills 1000 poultry
A new outbreak of bird flu has killed about 1000 poultry in northern China in the second such case in a week. Reportedly, 72 930 domestic poultry have been slaughtered and the outbreak is now under control. Laboratory tests had reportedly been confirmed the H5N1 strain of the virus. The outbreak, in Henan New Village in Yinchuan, Ningxia Hui region, follows a similar occurrence in neighbouring Inner Mongolia. Beijing banned chicken exports from the Baotou region of Inner Mongolia after H5N1 killed about 1000 chickens and ducks there. The Baotou outbreak, which came to light 27 Sep 2006, had been brought under control. It was the first incidence reported in China in 6 weeks. The latest case in Ningxia Hui brings to 40 the number of bird flu outbreaks among poultry in China since Oct 2005. China confirmed Aug 2006 that its first human bird flu victim died late 2003, 2 years earlier than previously reported.
(Promed 10/5/06)

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China (Inner Mongolia): Avian influenza H5N1 outbreak kills 1000 poultry
An outbreak of bird flu in north China's Inner Mongolia Autonomous Region has been put under control and no human infection was reported. As of 2 Oct 2006, no new deaths of poultry and no human cases of bird flu were reported. Nearly 1000 chickens and ducks reportedly died suddenly in a poultry farm in the village of Xincheng in the Jiuyuan District of Baotou city 27 Sep 2006. The national avian influenza laboratory later confirmed that the H5N1 virus was found in samples taken from the dead poultry.

The owner of the farm and his wife bought some 5400 chickens and ducks between 21 Aug and 20 Sep from other places in the county. The couple found more than 70 chickens and ducks dead in the evening of 20 Sep. Dead poultry were also found in the following days and the death toll rose to 985 as of 27 Sep, when the couple reported the case. Baotou city veterinarian station later reported the case and sent samples of the dead poultry to the Inner Mongolia Autonomous Regional Animal Epidemic Disease Control Center and the national avian influenza laboratory. The local agricultural department immediately quarantined the infected area. The owner and his wife were also quarantined and people who had close contact with them were under observation. To date, 17 616 chickens and ducks have been culled to control the outbreak. A batch of bird flu vaccines allocated by the Ministry of Agriculture reached Baotou. All poultry in Jiuyuan District will be inoculated in the next 10 days. An investigation is being conducted to find where the farm owner bought these chickens and ducks and where he sold the poultry.
(Promed 10/2/06)

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Indonesia (East Java): 69th human case of H5N1 avian influenza infection
As of 3 Oct 2006, the Ministry of Health in Indonesia has confirmed the country's 69th case of human infection with the H5N1 avian influenza virus. The case is a 21-year-old female from East Java Province. She developed symptoms 19 Sep 2006 and was hospitalized 25 Sep 2006. She remains hospitalized, and is also suffering from pneumonia. She is the sister of a confirmed H5N1 case, an 11-year-old male who died 18 Sep 2006. An Indonesian official said it was unlikely that the woman caught the virus from her brother. "They're genetically susceptible to the virus, which they were both exposed to from infected poultry," health ministry official I Nyoman Kandun said. Following that fatal case, health authorities initiated contact tracing, and 24 Sep 2006, they received reports of symptoms in the sister. In line with the national protocol, she was immediately given the antiviral drug, oseltamivir, and isolated in hospital. The source of her infection is presently under investigation. Poultry deaths in the family's household were noted both before and during the illness of the brother. The woman was likely exposed to these poultry as well as to her brother. Of the 69 cases confirmed to date in Indonesia, 52 have been fatal.
(Promed 10/4/06, CIDRAP 9/29/06 http://www.cidrap.umn.edu/)

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Indonesia: Healthy chickens test positive with H5N1 virus
A healthy chicken could be a carrier of the bird flu virus although it shows no symptoms of the illness. Head of the West Java Animal Husbandry Office, Rachmat Setiadi, said the warning was made following the discovery of healthy chickens that tested positive with H5N1 virus from a serology test conducted on 20 chickens around the house of 2 dead flu victims -- a 23-year-old man and his 20-year-old brother -- in Kebonwaru area, Batunggal. "The test has shown that 4 healthy chickens were infected with H5N1. . ." he said (However, finding a seroconversion in a healthy bird is not the same as proving that these birds are or are not capable of transmitting the virus). Currently, people are only made aware of the danger of bird flu when chickens die suddenly in their neighborhood. He said cases where healthy chickens were infected with bird flu had occurred not only in Bandung, but also in other cities and regencies. He recommended that residents stop keeping chickens in their backyards or near their houses. Out of Bandung's 26 cities and regencies, only 2 -- Tasikmalaya city and Ciamis regency -- are free of H5N1 virus in poultry. Meanwhile, serology tests on 11 dogs kept by the family of the bird flu cluster in Kebonwaru have came back negative. He said his office was currently working on a public campaign in 26 districts to make people aware of the threat of bird flu following these deaths.
(Promed 10/5/06)

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Indonesia: Avian influenza H5N1 may infect a quarter of Indonesia's domestic birds
Bird flu may have infected a quarter of backyard fowl in some of Indonesia's most densely populated areas, the country's top veterinary official said. Random tests carried out in areas where the virus is most prevalent on the island of Java detected the H5N1 influenza strain in as much as 27 percent of fowl and caged birds, said Director of Animal Health Musny Suatmodjo. He didn't say how many birds were tested or when the survey was done. Contact with infected birds risks spreading the disease to humans. The prevalence of H5N1 among Indonesia's 300 million poultry helps explain why the country accounts for 1-in-3 human deaths from the disease worldwide since 2003. "The backyard sector is the weakest link'' in controlling the virus, Suatmodjo said 27 Sep 2006. "The survey of hotspots in the backyard sector showed almost every flock has been previously infected,'' though not all birds show symptoms of the disease, he said.

Poultry are raised in the backyards of 80 percent of the country's 55 million households, according to the UN's Children's Fund. About 62 percent of Indonesian poultry are found on Java, where more than two-thirds of the country's human H5N1 fatalities have occurred. The virus has been found in fowl in 30 out of 33 provinces in the archipelago of 18,000 islands, making it difficult for disease trackers to detect outbreaks. The latest eruption was reported this month in the eastern province of North Sulawesi. "Wherever teams are carrying out active surveillance activities, they find the disease prevalent in poultry,'' said Christine Jost, chief technical adviser with the Food and Agriculture Organization's avian flu program in Indonesia. "The disease is endemic in many large islands of Indonesia like Java, Bali and Sumatra, where there is high prevalence of the disease and it is a great concern.''

Suatmodjo estimates that 10 percent of backyard poultry are vaccinated to prevent the disease. The agriculture ministry plans to introduce regulations next month requiring fowl be kept in coops, rather than being allowed to roam freely. Vaccinating and confining backyard poultry will work to stem the virus, said the FAO's Jost. The UN agency recommends people raising backyard poultry be encouraged to build night housing for their poultry. "It is of low cost, easy to maintain and is feasible to carry out interventions like vaccination when necessary,'' Jost said. A preventive vaccine campaign would require 1.2 billion doses of vaccines a year just for backyard chickens in Indonesia, she said. Given the country's "limited resources,'' the UN agency is "encouraging stakeholders to target resources'' at areas that would have the greatest chance of controlling the disease, she said. The agriculture ministry will need 90 million doses of avian flu vaccine next year to immunize backyard chickens, particularly in areas where the virus is most prevalent. Government funds may allow the ministry to buy as many as 60 million of doses, Suatmodjo said.
(Promed 9/29/06)

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Americas
USA (Illinois): Mild avian influenza virus found in ducks
Initial tests on wild ducks in Illinois suggest they have a low-pathogenic strain of avian influenza, not the deadly H5N1 strain. Viruses containing H5 and N1 surface proteins (hemagglutinin and neuraminidase) were found in samples from healthy migratory green-winged teals in Fulton County in west-central Illinois, the US Department of Agriculture (USDA) and the Department of the Interior said. The samples were collected Sep 24, 2006 in the Rice Lake Conservation area as part of an expanded wild bird monitoring program involving the USDA and the lower 48 states. Of 11 samples obtained from the ducks, 5 were positive for H5 and were sent to the USDA's National Veterinary Services Laboratory for confirmation. 1 of the 5 samples tested positive for both the H5 and N1 components. "However, this does not mean these ducks are infected with an H5N1 strain. It is possible that there could be two separate avian influenza viruses," the federal agencies said. Further testing at the NVSL will clarify if one or more of the virus strains are present, identify a specific subtype, and determine the pathogenicity. Results are expected in 2 to 3 weeks. Low-pathogenic avian influenza is common in wild birds and can be found in many duck populations, including green-winged teal. Low-pathogenic strains typically cause minor sickness or no noticeable symptoms.

Mild strains include the "North American" H5N1, which is different from the lethal H5N1 virus strains circulating in Asia, Europe, and Africa. However, low-pathogenic strains sometimes mutate into high-pathogenic forms. Since the USDA and DOI announced the expanded wild-bird monitoring program in early Aug, low-pathogenic H5N1 has been confirmed in Michigan, Maryland, and Pennsylvania. No birds in North America have tested positive for the Asian subtype of the H5N1 bird flu virus. Tests are pending on samples from pintail ducks in Montana, though initial results suggested a mild avian flu strain. Green-winged teals are commonly hunted, but there is no known health risk to hunters or hunting dogs from contact with low-pathogenic avian flu viruses.
(Promed 9/30/06, CIDRAP 10/2/06 http://www.cidrap.umn.edu/ )

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USA: Influenza workers seek to dispel vaccination myths
A powerful motivator for getting a seasonal influenza vaccine is having suffered through the misery of the disease. However, factors that sway people away from vaccination are a lack of information and outright misconceptions, the National Foundation for Infectious Diseases (NFID) found in a consumer survey. Julie Gerberding, director of CDC, said there will be 100 million seasonal influenza vaccine doses available this year, 17 million more than last year. However, Gerberding and other experts worry that Americans, particularly those with health risks, won't take full advantage of the increased supply. The study found that less than half of respondents (48%) planned to get a flu shot this year. The study, a random-dial telephone sample of 1,014 adults (503 men and 511 women) aged 18 and older, found that of the 52% who said they wouldn't get a flu shot, 43% didn't think influenza was serious enough to warrant vaccination. More than half of the respondents said they regarded a cold and influenza as similar health problems and would treat them similarly. 46% of respondents incorrectly thought that flu vaccine could cause the illness itself.

Better than half of those who planned to be immunized this year said they made vaccination a priority after suffering a bout of flu in a previous season. Study respondents knew that Sep through Nov is the best time to be immunized—but they erroneously believed that Dec is too late to benefit from the vaccine. The flu season peaks in Dec, Jan and Feb, sometime even in Mar, Susan J. Rehm, NFID medical director and vice chair of the Department of Infectious Diseases at the Cleveland Clinic, said. "The medical community must reinforce that later-season vaccination is useful, even if the disease has already begun in your area." Mark McClellan, administrator of the Centers for Medicare and Medicaid Services, said about a third of seniors don't get annual flu shots, even though vaccination is free through Medicare part B. He noted that each year, 200,000 people are hospitalized with influenza, and 36,000 die of the disease. Medicare officials are hoping to increase flu vaccination rates among seniors with a personalized, grassroots approach that focuses on preventive care, including vaccination and screening. Preventive services are now being promoted and delivered with the same system that administers the new Medicare prescription drug benefit, he said.

Another group on which health experts are focusing their flu vaccine message is parents of children aged 6 months to 5 years. Earlier this year, CDC added 2-, 3-, and 4-year-olds (and their household contacts) to its recommendations about who should receive the flu vaccine. Julia McMillan, a member of the American Academy of Pediatrics committee on infectious diseases and vice chair for pediatric education at Johns Hopkins University School of Medicine, said now is the time for parents to call their children's pediatrician to schedule an appointment for vaccination. "Rates aren't what they should be, especially in kids who have chronic conditions such as asthma," she said, noting that children who have chronic conditions are 5 times as likely as healthy children to be hospitalized with influenza.

Health officials also said they'd like to make people more aware of the CDC recommendation that pregnant women should receive flu shots. In the NFID survey, 49% thought that pregnant women should be vaccinated. Healthcare workers are another group with relatively low vaccination rates. Only 36% of healthcare workers are vaccinated each year; unvaccinated workers contribute to flu outbreaks and staffing shortages in health care facilities. CDC has issued stronger, earlier recommendations for healthcare workers, and in June the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) issued a new infection control standard that requires accredited organizations to offer flu immunizations to staff, volunteers, and others who have close contact with patients. The requirement takes effect Jan 1, 2007.

Gerberding said vaccine manufacturers will deliver 75 million doses of vaccine by the end of Oct 2006. Because vaccine distribution is handled by the private sector, coordination can be difficult. However, she added that the National Influenza Vaccine Summit, made up of 130 industry groups, has been working to resolve problems with supply and distribution.
(CIDRAP 10/4/06 http://www.cidrap.umn.edu/ )

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USA: FDA issues guide to ease production of cell-based vaccines
In a major push to modernize and speed the production of vaccines for pandemic influenza and other emerging threats, the US Food and Drug Administration (FDA) issued new guidance on how to safely and effectively develop new cell-based vaccines. The document, released Sep 28, updates 13-year-old guidelines on cell culture manufacturing, currently used to make vaccines for other diseases such as measles, mumps, and polio. The currently used egg-based method of producing influenza vaccines hasn't changed much in 50 years and is more laborious than cell culture production techniques. To produce a vaccine, the virus strain must be adapted to grow in eggs, and huge quantities of special fertilized eggs must be available. With cell culture technology, manufacturers grow vaccine components in human or animal cells so the viruses don't need to be adapted. Cells can be frozen and stored for use when needed, allowing production to be quickly ramped up in the event of an emergency. "The advice will assist manufacturers, including those that make influenza vaccine, both to develop new and better vaccines and to boost production capacity, making us better prepared for the threat of a future influenza pandemic and other infectious diseases," said Jesse Goodman, MD, MPH. Goodman directs the FDA Center for Biologics Evaluation and Research. The guidance helps vaccine makers determine the suitability of a cell culture for manufacturing, as well as test and validate the safety and purity of the cells. The document also advises when to test at different stages of production and defines quality-control testing methods for cell substrate and adventitious agents. The US Department of Health and Human Services (HHS) has made cell-based vaccine manufacturing a central focus of its pandemic plan. In May it awarded $1 billion among 5 companies to develop cell-based technologies for making flu vaccines. In Apr 2005, HHS awarded Sanofi Pasteur a $97 million contract to develop a cell-based flu vaccine. The company was the first to receive a federal contract for commercial-scale use of new flu vaccine technology. Last week, Sanofi Pasteur announced the launch of the first clinical trial of its first seasonal influenza vaccine made using cell culture technology.
(CIDRAP 10/2/06 http://www.cidrap.umn.edu/ )

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USA: FDA approves fifth flu vaccine--FluLaval
FluLaval has become the fifth influenza vaccine licensed by the US Food and Drug Administration (FDA) for use during the upcoming flu season. FluLaval, produced by ID Biomedical Corp. of Quebec, a subsidiary of GlaxoSmithKline (GSK), has been marketed in Canada under the brand name Fluviral since 2001. It was granted fast-track review status by the FDA Jul 2005. It is the second seasonal flu vaccine approved using an accelerated approval process, after GSK's Fluarix last year. FDA approval of FluLaval—for patients 18 years old or older—is projected to bring the total available number of doses to more than 110 million, according to CDC. The largest number of doses distributed in any year was 83.1 million, in 2003. About 81.2 million doses were distributed last year. The FDA cautions, however, that projections for total doses could change, because vaccine manufacturing is still under way.

"The challenges of vaccine supply in past flu seasons, the broadening CDC recommendations for annual vaccination, and the threat of a future avian flu pandemic all emphasize the value of adding more manufacturers and production capacity," said Jesse L. Goodman, director of the FDA's Center for Biologics Evaluation and Research. “The successful use of accelerated approval illustrates both the value of tools that FDA has put into place to meet critical public health needs, and the benefits of intensive scientific interactions between FDA and manufacturers and advice from FDA during product development and evaluation," he added.

During the approval process the FDA collected data from 2 clinical studies involving about 1,000 adults in the US and 658 patients who received the vaccine in Canada. The rate and nature of FluLaval's side effects were similar to those seen with other licensed seasonal flu vaccines. The agency said ID Biomedical showed that the vaccine induced levels of antibodies likely to prevent seasonal flu. In line with the approval process, the company will conduct further studies to verify that the vaccine reduces the risk of flu. FluLaval contains inactivated viruses (which cannot cause the disease) and is administered as a single injection in the upper arm. It is packaged in a multi-dose vial with thimerosal, a mercury derivative, as a preservative. GSK plans to develop a reduced-thimerosal or thimerosal-free formulation for studies in children. FluLaval has not been studied in children and pregnant women. Besides FluLaval and Fluarix, the other FDA-approved seasonal flu vaccines are Fluzone (Sanofi Pasteur), FluMist (MedImmune), and Fluvirin (Novartis).
(CIDRAP 10/5/06 http://www.cidrap.umn.edu/ )

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1. Articles
Groups call for pandemic flu vaccine 'master plan'
Public health and infectious disease experts called on the US to develop a "master plan" for development of pandemic influenza vaccines in order to translate scientific advances more rapidly into improved pandemic preparedness. The recommendation was 1 of 7 pandemic policy suggestions made by the Trust for America's Health (TFAH), a nonprofit public health advocacy group, and the Infectious Diseases Society of America (IDSA). "The United States must expand and accelerate research efforts and ensure we rapidly translate scientific breakthroughs into real-world practice to prepare for a possible pandemic," Kathleen Maletic Neuzil, MD, coauthor of the report, said. She is chair of the IDSA's Pandemic Influenza Task Force and an associate professor of medicine at the University of Washington School of Medicine. The 2 organizations also called for streamlining the licensing process for pandemic flu vaccines, developing a nationwide system to track the use and effectiveness of seasonal flu vaccine, and relieving states of cost-sharing for the nation's stockpile of antiviral drugs, among other measures.

The recommendations are part of a 26-page report, "Pandemic Influenza: The State of the Science," released by the two groups. The report discusses the threat posed by H5N1 and other avian influenza viruses and outlines the status of efforts to develop vaccines, drugs, and diagnostic techniques for pandemic flu. "An effective US vaccine research and development strategic program must be much larger in scale than current funding permits, in addition to being multinational in scope," the report states. It describes current vaccine development efforts as a "patchwork" that may not produce rapid progress.

The groups called for a "Pandemic Vaccine Research and Development Master Plan to systemize and greatly enhance the current U.S. and international vaccine research and development strategies, bringing together the knowledge of government and private industry scientists." The master plan should include an inventory of all relevant issues and all activities already under way. The plan should state which sectors are responsible for completing each activity, list funding needs, and provide benchmarks for measuring progress. The vaccine effort would require a "substantial" increase in funding, the groups say. TFAH Executive Director Jeffrey Levi declined to name a figure, saying the plan must be developed before its cost can be estimated. "We recognize that Congress over the last year has invested more than $5 billion toward improving pandemic preparedness," but that is only a starting point for vaccine development and production, Levi said. In response to questions, Levi said he was uncertain if any legislation would be needed to pave the way for the suggested master plan. In working on HIV and AIDS, he said, "Government found a way to convene the academic community and patients and the private sector to talk about issues and share information without violating intellectual property rights."

Levi and Neuzil were asked if they could say which vaccines now in development are most promising. Neuzil responded that it's difficult to assess the vaccines, because many vaccine trials have been described only in press releases so far, and even scientific journal articles don't always give full technical data. "From my perspective it's a bit like comparing apples and oranges, because the data I have on each vaccine are in no way equivalent," said Neuzil. But what is clear, she said, is that "with H5N1 it's likely we'll need more than 1 dose of vaccine, and we'll need either a high concentration of antigen or we'll need an adjuvant".

The 2 groups endorse the US government goal of stockpiling enough doses of antiviral drugs to cover about 25% of the population (81 million treatment courses), but they take issue with the funding mechanism. The federal plan calls for buying 50 million treatment courses, but making the states responsible for buying the other 31 million courses, with a 25% federal subsidy. Levi said the federal government should pay for all 81 million courses. "We need to make sure that every state has the right amount, and not every state is going to be able to afford that," he said. "We believe this is a federal responsibility, and therefore the federal government should purchase it and stockpile it."

The TFAH-IDSA report also makes the following recommendations:
• CDC should implement a nationwide, real-time system to track flu vaccine efficacy, distribution and redistribution, uptake, and impact.
• The US should boost surveillance for novel flu viruses by expanding working relationships with other countries, especially in Southeast Asia, through WHO.
• The nation should embrace policies to increase seasonal flu vaccination in order to reduce the toll of flu and to stabilize vaccine manufacturing capacity. This should include developing "standardized templates for conducting mass vaccinations and countermeasure distribution."
• The Food and Drug Administration (FDA) should streamline the licensing process for pandemic vaccines, using a different approach than with season flu vaccines.
• The FDA should adopt criteria for accepting foreign clinical trial data for registering flu vaccines in the US.

An additional recommendation is that Congress pass the proposed Pandemic and All-Hazards Preparedness Act to improve public health capabilities and support private-sector innovation.

The report was written by Levi and Neuzil with Marlene Cimons, an adjunct journalism professor at the University of Maryland's Philip Merrill College of Journalism. In preparing the report, they drew on interviews with 14 leading experts on flu, pandemics, and infectious disease, including Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases. The group also included Michael T. Osterholm, director of the University of Minnesota Center for Infectious Disease Research and Policy, publisher of the CIDRAP Web site.
(CIDRAP 10/4/06 http://www.cidrap.umn.edu/ )

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Injectable drug seen as potential treatment for influenza, both seasonal and avian
Recent tests suggest that an antiviral drug given by intravenous (IV) or intramuscular (IM) injection could eventually serve as another weapon against influenza. In animal studies, peramivir improved survival in mice and ferrets infected with H5N1 avian flu, according to BioCryst Pharmaceuticals Inc., which is developing the drug. The results were presented Sep 30, 2006 at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). In addition, in phase 1 clinical studies, IV and IM doses of peramivir produced high blood levels of the drug in human volunteers without causing any adverse events, according to Charles E. Bugg, chairman and chief executive of BioCryst. The clinical studies "showed you can achieve high blood levels in humans safely," Bugg said. The combination of those results with the animal studies is promising, he said. Peramivir is a neuraminidase inhibitor, like the licensed antivirals oseltamivir (Tamiflu), and zanamivir (Relenza). Oseltamivir is an oral drug, while zanamivir is inhaled as a powder. Many countries have stockpiled oseltamivir on the assumption that it will help if the H5N1 virus sparks a pandemic.

BioCryst started developing peramivir in 1998 in partnership with Johnson and Johnson. Early studies showed the drug inhibited flu viruses effectively, but when taken orally, its bioavailability was very low. Because injectable peramivir looked promising in animals, the program was resurrected. The company is developing an IV formulation intended for hospital patients and an IM formulation for outpatients.

In the animal studies, 4 groups of mice were infected with an H5N1 virus and then were treated with either a single IM injection of peramvir, 5 daily IM injections, oral oseltamivir for 5 days, or an IM placebo injection daily for 5 days. The single-injection group had a 70% survival rate and the 5-injection group a 80% survival rate, compared with 36% for the placebo group and 70% for the oseltamivir group. In the ferret experiment, 1 group received a daily IM injection for 5 days, while a second group received an IM placebo daily for 5 days. 86 percent of the treated group survived, versus 43% of the placebo group. Bugg said treatment was started an hour after the animals were infected with the virus. He said additional studies will involve longer time lapses between exposure and the start of treatment.

Results of the clinical studies were presented by flu expert Frederick Hayden, of the University of Virginia. 3 groups of volunteers received different IV doses of peramivir, and a fourth group received increasing IM doses once a day for 3 days. "Preliminary safety results indicate that in the 4 studies, all doses were well-tolerated with no adverse laboratory events or ECG findings reported," the statement said. Hayden said that injecting peramivir into the bloodstream or into muscle can produce blood levels 100 times higher than those seen wit oral oseltamivir, now considered the most promising treatment for H5N1 infection. Bugg said it would take at least several more years to gain FDA approval.

Bugg said plans also call for testing the drug in human H5N1 patients at sites in Thailand and Vietnam and also to make it available in Turkey. "We'll be trying to collect data from H5N1-infected patients in Southeast Asia in collaboration with the World Health Organization," he said. "We'll be on the front line to capture H5N1 if it occurs. But realistically we won't have enough [patients] for a meaningful statistical analysis." Bugg said peramivir is easier to make than Tamiflu. One Swiss manufacturer can make 1 metric ton of the drug in a month, enough to treat an estimated 8 million people, he said.
(CIDRAP 10/2/06 http://www.cidrap.umn.edu/ )

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Airborne influenza viruses threaten health workers, expert says
A microbiologist who reviewed the evidence about how influenza viruses spread says that some official guidelines, including the US pandemic influenza plan, may not go far enough in protecting healthcare workers who take care of flu patients. Writing in Emerging Infectious Diseases, Raymond Tellier of the University of Toronto says there is good evidence that flu viruses often spread via tiny airborne particles, despite a common belief that they travel mainly in large droplets that quickly fall to the ground after a flu patient coughs or sneezes. Good protection from airborne particles requires the use of an N95 respirator. Yet the US, Canadian, and British pandemic flu plans advise healthcare workers to use simple surgical masks, which are much less effective, Tellier contends.

"Compelling evidence in the literature indicates that aerosol transmission of influenza is an important mode of transmission, which has obvious implications for pandemic influenza planning, and in particular for recommendations about the use of N95 respirators as part of personal protective equipment," he writes. "Airborne particles" are usually defined as particles about 5 microns or less in diameter, Tellier says. Particles larger than about 10 to 20 microns fall quickly to the ground, while those smaller than 3 microns essentially do not settle. Coughing and sneezing generate particles in a range of sizes, many of them small enough to stay airborne for a long time. Airborne particles can penetrate into the lungs, whereas the larger particles and droplets are more likely to be trapped in the upper respiratory tract.

Experiments have shown that mice, monkeys, and human volunteers can be infected by exposure to aeorosol flu viruses, according to Tellier. In addition, various epidemiologic observations indicate that aerosol transmission is important. Tellier says many guidelines and review articles state that large droplets appear to be the main vehicle for flu virus transmission, but they offer little supporting evidence. "Despite extensive searches, I have not found a study that proves the notion that large-droplets transmission is predominant and that aerosol transmission is negligible (or nonexistent)," he writes. Further, he says, infection control experts often argue that large-droplet precautions have proved adequate to stop flu outbreaks. But he contends that several factors cast doubt on the evidence for this view. For example, without laboratory diagnosis, what is believed to be a flu outbreak can be some other virus; serologic studies often are omitted, and asymptomatic flu infections in healthcare workers are probably missed; many people have partial immunity to seasonal flu viruses; and surgical masks provide some limited protection against aerosols.

Tellier goes on to say that evidence suggests that current strains of H5N1 avian influenza predominantly infect the lower respiratory tract, which in turn suggests that airborne particles are involved. "Given the strong evidence for aerosol transmission of influenza viruses in general, and the high lethality of the current strains of avian influenza A (H5N1), recommending the use of N95 respirators, not surgical masks, as part of the protective equipment seems rational," he states. The current US pandemic influenza plan, according to Tellier, "acknowledges the contribution of aerosols in influenza but curiously recommends surgical masks for routine care; the use of N95 respirators is reserved for 'aerosolizing procedures.'" In contrast, CDC's current infection control guidelines for healthcare facilities treating avian flu patients say that workers should use a fit-tested respirator at least as good as the N95 type when in a patient's room. Reportedly, the infection control guidance in the US pandemic flu plan is being updated.

Tellier R. Review of aerosol transmission of influenza A virus. Emerg Infect Dis 2006 Nov;12(11)
(CIDRAP 9/29/06 http://www.cidrap.umn.edu/ )

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Seasonal and Pandemic Influenza: Recommendations for Preparedness in the United States
Richard J. Whitley, et al.
The Journal of Infectious Diseases. 2006;194:S155-S161
Abstract: “There is a continued need to improve the state of preparedness for a potential influenza pandemic in the United States despite the publication of a pandemic influenza plan by the Department of Health and Human Services. Of particular importance are the sense of urgency for a coordinated response plan, an allocation of adequate funds to deal with this issue, and the need for a national leader to coordinate the development and execution of a national plan, including its relationship to the control of seasonal influenza. In addition, an infrastructure needs to be established in the United States to enable the rapid development and large-scale production of a safe and effective vaccine for new influenza strains; methods to treat influenza pneumonia need to be evaluated; a coordinated public health response needs to be defined; a nationally developed blueprint to deal with logistics of pandemic prevention is required; and there is a need to establish reliable communication systems on a national and local basis, to provide accurate information to the lay public, health care workers, and the agricultural sector.”

*** “Seasonal and Pandemic Influenza: At the Crossroads, a Global Opportunity”—The Nov 1, 2006 supplement to The Journal of Infectious Diseases is dedicated to this topic: http://www.journals.uchicago.edu/JID/journal/contents/v194nS2.html.
(CIDRAP http://www.cidrap.umn.edu/ )

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Childhood Influenza Vaccination Coverage --- United States, 2004--05 Influenza Season
“Children aged <2 years are at increased risk for influenza-related hospitalizations, and children aged 24--59 months are more likely than older children to visit a clinic, hospital, or emergency department with influenza-associated illness. In 2002, the Advisory Committee on Immunization Practices (ACIP) encouraged annual influenza vaccinations for children aged 6--23 months (and for household contacts of and out-of-home caregivers for children aged <2 years). For the 2004--05 influenza season, ACIP strengthened its encouragement to a full recommendation. For the upcoming 2006--07 influenza season, ACIP has further extended its recommendation to include all children aged 6--59 months (and their household contacts and out-of-home caregivers). Others recommended to receive influenza vaccination include children aged 6--18 years who have certain high-risk medical conditions, are on chronic aspirin therapy, or who are household contacts of persons at high risk for influenza complications. This report provides an assessment of influenza vaccination coverage among children aged 6--23 months during the 2004--05 influenza season. The findings demonstrate that vaccination coverage in that age group approximately doubled from the 2003--04 influenza season, with substantial variability among states and urban areas. However, the percentage of fully vaccinated children remained low, underscoring the need for increased measures to improve pediatric vaccination coverage and ongoing monitoring of coverage among young children and their close contacts. . .” http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5539a1.htm
(MMWR October 6, 2006 / 55(39);1062-1065)

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Influenza and pneumococcal vaccination coverage among persons aged >65 Years--United States, 2004--2005
“Vaccination of persons at increased risk for complications from influenza and pneumococcal disease is a key public health strategy in the United States. During the 1990--1999 influenza seasons, approximately 36,000 deaths were attributed annually to influenza infection, with approximately 90% of deaths occurring among adults aged >65 years. In 1998, an estimated 3,400 adults aged >65 years died as a result of invasive pneumococcal disease. One of the Healthy People 2010 objectives is to achieve 90% coverage of noninstitutionalized adults aged >65 years for both influenza and pneumococcal vaccinations (objective 14-29). To assess progress toward this goal, this report examines vaccination coverage for persons interviewed in the 2004 and 2005 Behavioral Risk Factor Surveillance System (BRFSS) surveys. The 2004--05 influenza season was characterized by an influenza vaccine shortage. As a result, the Advisory Committee on Immunization Practices (ACIP) issued recommendations that influenza vaccine be reserved for persons in priority groups, including persons aged >65 years, and that others should defer vaccination until supply was sufficient. The results of this assessment indicated that, overall, influenza vaccination coverage was lower in the 2005 survey year than in 2004, whereas pneumococcal vaccination coverage was nearly unchanged from 2004 to 2005. In both years, influenza and pneumococcal vaccination coverage varied from state to state. Continued measures are needed to increase the proportion of older adults who receive influenza and pneumococcal vaccines; health-care providers should offer pneumococcal vaccine all year and should continue to offer influenza vaccine during December and throughout the influenza season, even after influenza activity has been documented in the community. . .”
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5539a2.htm
(MMWR October 6, 2006 / 55(39);1065-1068)

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2. Notifications
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 the latest issue of FAOAIDEnews, a situation update on avian influenza outbreaks throughout the world. Also new are “Learning By Doing’ is Key to Disease Control in Poultry”, 25 Sep 2006.
- OIE: http://www.oie.int/eng/en_index.htm.
- US CDC: http://www.cdc.gov/flu/avian/index.htm
- The US government’s web site for pandemic/avian flu: http://www.pandemicflu.gov/.
- 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 update--Avian influenza backgrounder.
- US Geological Survey, National Wildlife Health Center Avian Influenza Information: http://www.nwhc.usgs.gov/disease_information/avian_influenza/index.jsp. Very frequent news updates.
(WHO; FAO, OIE; CDC; CIDRAP; PAHO; AVMA; USGS)

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 apecein@u.washington.edu