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EINet Alert ~ Jan 16, 2009


*****A free service of the APEC Emerging Infections Network*****
APEC EINet News Briefs offers the latest news, journal articles, and notifications for emerging infections affecting the APEC member economies. It was created to foster transparency, communication, and collaboration in emerging infectious diseases among health professionals, international business and commerce leaders, and policy makers in the Asia-Pacific region.
In this edition:

1. Influenza News
- Cumulative number of human cases of avian influenza A/(H5N1)
- South Korea: Reports first oseltamivir-resistant A/H1N1 case
- India (Manipur): Mysterious illness among 32 villagers
- USA: HHS reports progress on cell-based pandemic vaccines
- USA: Novartis gets US contract for cell-based influenza vaccine plant
- USA (South Dakota): Man infected with swine influenza
- Egypt: Child infected with avian influenza H5N1
- USA: Study finds influenza vaccine benefits older workers

2. Updates
- AVIAN/PANDEMIC INFLUENZA

3. Articles
- Measurement of Airborne Influenza Virus in a Hospital Emergency Department
- Neuraminidase Inhibitor Resistance after Oseltamivir Treatment of Acute Influenza A and B in Children

4. Notifications
- CDC Statement on Oseltamivir (Tamiflu) Resistance and Antiviral Recommendations
- Getting beyond getting ready for pandemic influenza
- Assessment of States’ Operating Plans to Combat Pandemic Influenza


1. Influenza News

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

2009
Egypt/ 1(0)
Total/ 1(0)

2008
Bangladesh / 1 (0)
Cambodia/ 1 (0)
China / 4 (4)
Egypt / 8 (4)
Indonesia / 22 (18)
Viet Nam / 6 (5)
Total / 42 (31)

***For data on human cases of avian influenza prior to 2009, go to:
http://depts.washington.edu/einet/humanh5n1.html Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 394 (248).
(WHO 1/14/09 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 1/9/09) WHO's maps showing world's areas affected by H5N1 avian influenza (last updated 12/24/08):
http://gamapserver.who.int/mapLibrary/ WHO’s timeline of important H5N1-related events (last updated 1/5/09):
http://www.who.int/csr/disease/avian_influenza/ai_timeline/en/index.html

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Asia
South Korea: Reports first oseltamivir-resistant A/H1N1 case
The Korean Centre for Disease Control (CDC) reported on 9 Jan 2009 that oseltamivir-resistant A/H1N1 strains have been found through the Korean Influenza Surveillance Scheme (KISS) during the period from 7 Sep to 13 Dec 2008. This is the first case of oseltamivir-resistant A/H1N1 in Korea.

The Korean CDC performed both genetic and phenotypic analysis of the neuraminidase gene of Korean isolates during the 2008-2009 season for the monitoring of drug resistance. From 7 Sep to 13 Dec 2008, a total of 244 influenza viruses (220 A/H1N1 and 24 A/H3N2) were isolated, and 17 A/H1N1 (7.7 per cent, 17/220) and 10 A/H3N2 (41.7 per cent, 10/24) were tested for oseltamivir and zanamivir resistance. They found 16 oseltamivir-resistant A/H1N1 (94.1 per cent, 16/17) and could not find any oseltamivir-resistant A/H3N2 strains. There were no isolates resistant to zanamivir among 27 viruses (0.0 per cent, 0/27).

They also tested amantadine-resistance for these isolates (17 A/H1N1 and 10 A/H3N2). The rate of resistance against amantadine of A/H1N1 and A/H3N2 was 5.9 per cent (1/17) and 100 per cent (10/10), respectively.
(ProMED 1/13/09)

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India (Manipur): Mysterious illness among 32 villagers
The Manipur State Authority has yet to confirm the mysterious disease that spread among the villagers of Churachandpur district on 8 Jan 2009. The sudden deaths of 17 chickens and subsequent hospitalization of 32 villagers, mostly women, with a mysterious illness since 4 Jan 2009 has evoked a bird flu scare in the district, particularly in the affected Misao Lhahvom village, 72 km south of the state capital.

Though experts confirmed that there's no evidence of bird flu in birds in the area, they're still collecting blood samples of the hospitalized villagers to verify the disease.

According to an employee of Churachandpur district hospital, most of the patients admitted there complained of high fever followed by unconsciousness. Presently, 28 patients were given treatment at the hospital after 10 of them were discharged, he added.

Locals believe that the cause of the disease might be related to food poisoning in the recent Christmas celebration. However, Dr Motilal, director of state health services, said it was a viral fever.
(ProMED 1/9/09)

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Americas
USA: HHS reports progress on cell-based pandemic vaccines
In a progress report on federal pandemic influenza planning efforts, the US Department of Health and Human Services (HHS) says several companies working under federal contracts are on track to develop cell culture–based pandemic flu vaccines. The report, released on 8 Jan 2009, also says that biotechnology companies hope to have point-of-care tests that can distinguish between pandemic and seasonal flu viruses ready to submit to the Food and Drug Administration (FDA) by the end of this year.

The report is the sixth progress update since March 2006 and comes as Leavitt nears the end of his tenure as secretary. In his introduction, Leavitt wrote that HHS has accomplished a great deal over the past 33 months but still has much to do. "Preparation is a continuum. Each day that we prepare brings us closer to being ready," he said.

The report says that all six companies that HHS contracted with in 2006 to develop cell-based flu vaccines are moving toward FDA approval of their vaccines and that five are on target for reaching their contract milestones. "Contracts with six manufacturers are leading to the capacity for US-based production of at least 240 million courses of cell-based pandemic vaccine within six months of the emergence of a pandemic influenza virus," Leavitt wrote.

In August 2008 HHS sought proposals to build domestic facilities to make seasonal and pandemic cell-based vaccines, and the agency hopes to award $500 million in contracts during fiscal year 2009. The agency is still reviewing proposals it received in 2007 to develop a next-generation DNA-based influenza vaccine and plans to issue a second request for proposals for recombinant vaccine development.

As of September the federal stockpile of prepandemic H5N1 flu vaccine contained enough to vaccinate 12.2 million people. In 2005 the agency set a goal of having enough vaccine for 20 million people.

The agency has said it hopes to stretch the nation's pandemic vaccine supply beyond initial projections by pairing it with adjuvants, additives designed to stimulate a stronger immune response and perhaps provide broader protection against a range of influenza strains. HHS, based on early research, has considered the possibility of combining an H5N1 vaccine made by one company with adjuvants from another company. The agency stated further research is underway to test the "mix-and-match" approach.

In the meantime, HHS will continue adding prepandemic vaccine doses to the national stockpile and will move forward with buying 5.2 million doses of a GlaxoSmithKline adjuvant that it will pair with the government's existing supply of GlaxoSmithKline bulk antigen.

The new point-of-care influenza rapid tests will allow healthcare workers in outpatient settings to distinguish quickly between seasonal and pandemic influenza. Clinical trials will start soon, and manufacturers hope to submit the devices for FDA approval by the end of 2009. The agency also said it expects to award contracts for a more reliable specimen collection system by the end of the year.

HHS has a goal of ensuring that the nation has a sufficient supply of antiviral drugs for 25% of the population. In December 2007, HHS met its goal of buying 50 million treatment courses of oseltamivir and zanamivir. Federal officials want states to buy enough doses, with a 25% federal subsidy, to treat another 31 million people, but so far they have purchased only 23 million courses through the program, of which 22 million have been delivered. As an outgrowth of federal efforts to improve global disease surveillance and laboratory capacity and training, HHS reported that China has improved its monitoring of this year's seasonal influenza cases and can now report cases weekly. "This increased level of surveillance will help lead to a quicker identification of a pandemic influenza strain, should it appear in China," the report says.

Officials have boosted federal stockpiles of personal protective equipment to 158 million masks and respirators and have allocated $100 million toward ventilators, syringes, intravenous antibiotics, gloves, gowns, and other supplies that would be needed during an influenza pandemic, Leavitt wrote. He said HHS received public comments in June on its preliminary guidance on mask and respirator use and expects to release the final document in 2010.
(CIDRAP 1/9/09)

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USA: Novartis gets US contract for cell-based influenza vaccine plant
The US government has awarded Novartis a $487 million contract to help build a plant in North Carolina that the company says will be capable of producing 150 million doses of cell-based pandemic influenza vaccine within six months after the start of a pandemic.

Because of the advantages of growing flu vaccines in cell culture instead of in chicken eggs, the conventional method, the Novartis facility is expected to increase the US capacity to make pandemic flu vaccine by 25%, the Department of Health and Human Services (HHS) said.

The facility, which is already under construction in Holly Springs, N.C., also will make prepandemic flu vaccines, HHS said. The contract calls for HHS and Novartis to share the cost of the facility, with HHS providing 40% and the company paying 60%.

Under the contract, Novartis is to supply "two commercial-scale lots" of prepandemic vaccine per year for three years, according to the company announcement. Robinson said that could amount to at least 3 million doses per year and explained that the contract actually provides for either seasonal or prepandemic cell-based vaccine. The contract also gives HHS the option to continue buying vaccine for 17 more years.

Novartis already makes a cell-based seasonal flu vaccine that was approved by the European Union in May 2008, Robinson noted. He said the company also has applied to the EU for licensure of a cell-based H5N1 prepandemic vaccine.

The HHS statement said, "Cell-based vaccine production could more easily meet surge capacity needs because cells could be frozen and stored in advance of an epidemic or developed rapidly in response to an epidemic. Cell-based vaccine production also dramatically reduces the possibility for contamination and promises to be more reliable, flexible, and expandable than egg-based methods."
(ProMED 1/15/09)

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USA (South Dakota): Man infected with swine influenza
Public health officials from South Dakota reported a swine influenza infection in a 19-year-old male college student on 14 Jan 2009, the second case in the United States in the past 2 months.

The South Dakota Department of Health (SDDH) said that the patient got sick five weeks ago and that the state's public health laboratory had identified the influenza A/H1 portion of the virus and that the US Centers for Disease Control and Prevention (CDC) identified the swine components of the virus.

The CDC typically receives about one report of a human swine flu case a year. In late November 2008, the CDC reported on a patient from Texas who was infected with swine influenza after exposure to pigs, including a sick one.

Lon Kightlinger, PhD, epidemiologist for the SDDH, said in the statement that swine influenza in humans is rare. "Most often the cases occur in people with direct exposure to pigs, such as swine farm workers," he said. "Human-to-human transmission is very rare." Kightlinger said that an investigation into the source of the man's illness did not reveal direct contact with pigs; however, officials are exploring whether he had indirect contact.

Human infections with novel influenza A subtypes now are nationally notifiable diseases in the United States. In a recent report in the September 2008 issue of Emerging Infectious Diseases on a 2005 Wisconsin case, the authors wrote that triple reassortant H1N1 subtypes are the predominant genotype in North American pigs and that human swine flu illnesses often mimic seasonal flu infections. They recommended that clinicians ask patients with unexplained influenza-like illnesses about exposure to animals, including pigs, and visits to petting zoos and county fairs.

The CDC had noted that swine flu outbreaks in pigs typically occur in late fall and winter and that seasonal influenza vaccines are likely to partially protect against swine H3N2 viruses, but not the H1N1 subtype.
(CIDRAP 1/15/09)

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Africa
Egypt: Child infected with avian influenza H5N1
A 21-month-old Egyptian girl has been hospitalized with an H5N1 avian influenza infection, the country's health ministry said on 12 Jan 2009. The World Health Organization (WHO) indicated that the girl's symptoms started on 9 Jan 2009 and she was admitted the next day to Imbaba Fever Hospital with fever, cough, vomiting, diarrhea, and rapid respiration. Her illness is listed as Egypt's 52nd H5N1 case.

The patient is from Kerdasa district, in 6th of October governorate on the western outskirts of Cairo. Her medical team immediately suspected avian influenza and treated the girl with oseltamivir (Tamiflu), 40 hours after the onset of her symptoms, according to the WHO report.

An investigation into the source of the girl's infection suggests that she had close contact with sick and dead poultry before she got sick. The girl is recovering and is in good health.

Egypt reported its last human H5N1 case in early Dec 2008, in a 16-year-old girl from Asyut governorate who died on 15 Dec 2008 after exposure to sick and dead poultry in her household. The WHO listed the girl as Egypt's 51st case and its 23rd death.

Meanwhile, veterinary authorities in Egypt recently reported avian influenza outbreaks among backyard birds in two governorates, according to recent updates that appeared on the Egypt-based Strengthening Avian Influenza Detection and Response (SAIDR) Website. SAIDR, a project funded by the US Agency for International Development with assistance from Johns Hopkins University, is designed to help Egypt coordinate avian flu efforts with its international partners.

One of the outbreaks, reported on 31 Dec 2008, occurred in Fayoum governorate in central Egypt, where the virus struck 36 birds, including chickens, geese, and ducks that had been vaccinated in August 2008. The other outbreak, reported on 9 Jan 2009, occurred in Menofia governorate in northern Egypt, where the virus hit 34 previously vaccinated chickens and ducks.

The H5N1 virus is endemic in Egyptian poultry. The country's last report to the World Organization for Animal Health (OIE) in mid-June 2008 detailed an outbreak in backyard birds in Luxor governorate.
(CIDRAP 1/13/09)

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USA: Study finds influenza vaccine benefits older workers
Workers ages 50 to 64 that get their annual flu shots miss less work and experience less of a productivity drop-off than those who don't, according to a new study, findings that might help public officials lift immunization rates among this age-group.

Authors from the Minneapolis Veterans Affairs Medical Center and the University of Minnesota, who published their report in the Feb 1 issue of Clinical Infectious Diseases (CID), wrote that scarce information on the impact of the flu and on the benefits of vaccination in this age-group might be one reason for low vaccination rates in this group. Workers in this age range have been targeted for influenza vaccines since the 2000-2001 flu season.

The true cost of influenza
Previous studies on the benefits of the flu vaccine for working adults were based mainly on those younger than 50, the authors reported, pointing out that their findings demonstrate that the 50-to-64 age-group can reap the same benefits from immunization as other adult populations.

They pointed out that costs associated with lower work productivity are an important economic burden linked to influenza. They calculated that for each worker, vaccination prevented a mean of .37 work days lost and a mean of 1.45 days of working while ill.

"Studies that fail to account for presenteeism [working while sick] in their estimates of economic burden of influenza may substantially underestimate the impact of illness and the productivity benefits associated with vaccination," the group wrote.

Implications for public health policy
In an editorial comment on the study, Gregory A. Poland, MD, a vaccine expert at the Mayo Clinic in Rochester, Minn., wrote that the vaccination payoff the group found "was a huge benefit when the public health impact is considered."

An often-overlooked aspect of presenteeism is safety, he wrote, and working while sick may impair the functioning and judgment in, for example, pilots, physicians, nurses, and law-enforcement officers.
(CIDRAP 1/14/09)

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

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3. Articles
Measurement of Airborne Influenza Virus in a Hospital Emergency Department
Blachere FM et al. Clinic Infect Dis. 9 Jan 2009. Available at http://www.journals.uchicago.edu/doi/abs/10.1086/596478.

Abstract
Size fractionated aerosol particles were collected in a hospital emergency department to test for airborne influenza virus. Using real-time polymerase chain reaction, we confirmed the presence of airborne influenza virus and found that 53% of detectable influenza virus particles were within the respirable aerosol fraction. Our results provide evidence that influenza virus may spread through the airborne route.

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Neuraminidase Inhibitor Resistance after Oseltamivir Treatment of Acute Influenza A and B in Children
Stephenson I et al. Clinic Infect Dis. 9 Jan 2009. Available at http://www.journals.uchicago.edu/doi/abs/10.1086/596311.

Background. Oseltamivir, a specific influenza neuraminidase inhibitor, is an effective treatment for seasonal influenza. Emergence of drug-resistant influenza viruses after treatment has been reported, particularly in children in Japan, where the dosing schedule is different from that used throughout the rest of the world. We investigated the emergence of drug-resistant infection in children treated with a tiered weight-based dosing regimen.

Methods. We analyzed sequential clinical nasopharyngeal samples, obtained before and after tiered weight-based oseltamivir therapy, from children with acute influenza during 2005–2007. We isolated viruses, tested for drug resistance with use of a fluorescence-based neuraminidase inhibition assay, performed neuraminidase gene sequencing, and determined quantitative viral loads.

Results. Sixty-four children (34 with influenza A subtype H3N2, 11 with influenza A subtype H1N1, and 19 with influenza B virus) aged 1–12 years (median age, 3 years, 1 month) were enrolled. By days 4–7 after initiation of treatment, of 64 samples tested, 47 (73.4%) and 26 (40.6%) had virus detectable by reverse-transcriptase polymerase chain reaction and culture, respectively. By days 8–12 after initiation of treatment, of 53 samples tested, 18 (33.9%) and 1 (1.8%) had virus detectable by reverse-transcriptase polymerase chain reaction and culture, respectively. We found no statistically significant differences in the reduction of viral shedding or time to clearance of virus between viral subtypes. Antiviral-resistant viruses were recovered from 3 (27.3%) of 11 children with influenza A subtype H1N1, 1 (2.9%) of 34 children with influenza A subtype H3N2, and 0 (0%) of 19 children with influenza B virus, all of whom were treated with oseltamivir. There was no evidence of prolonged illness in children infected with drug-resistant virus.

Conclusions. Drug resistance emerges at a higher rate in influenza A subtype H1N1 virus than in influenza A subtype H3N2 or influenza B virus after tiered weight-based oseltamivir therapy. Virological surveillance for patterns of drug resistance is essential for determination of antiviral treatment strategies and for composition of pandemic preparedness stockpiles.

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4. Notifications
CDC Statement on Oseltamivir (Tamiflu) Resistance and Antiviral Recommendations
Press release on 9 Jan 2009

On December 19, 2008, the US Centers for Disease Control and Prevention (CDC) issued interim guidance for health care professionals on the use of influenza antiviral medications this flu season. The guidance was issued in response to early data from a limited number of states indicating that a high proportion of influenza A (H1N1) viruses are resistant to the influenza antiviral medication oseltamivir (Tamiflu). Worldwide, the proportion of H1N1 viruses that are resistant to oseltamivir has been increasing so this development is not surprising.

Recent media reports may have led some to believe that these developments mean physicians are without influenza treatment options for the 2008-2009 flu season.

At this time, it’s not possible to predict how common H1N1 viruses will be during the rest of this flu season, as there are many different flu viruses and every influenza season is different. The current samples studied come from a handful of states, and may not be indicative of how the rest of the season will progress or what viruses will circulate in other states. However the circulation of oseltamivir-resistant viruses does have treatment implications for health care professionals. CDC is continuing to monitor this situation very closely, but has issued interim guidance for health care professionals to guide their treatment decisions in the current situation.

In fact, the interim CDC guidance provides advice for clinicians on how to treat patients with influenza antiviral medications this season. Clinicians can use influenza test results and information, if available, about which viruses are circulating, to help decide which antiviral(s) should be used. If H1N1 viruses are circulating in the community, or it’s not clear which viruses are circulating, health care providers are recommended to use an alternative antiviral, zanamivir (Relenza), or to use combination therapy of oseltamivir and rimantadine. Use of zanamivir or dual therapy with oseltamivir and rimantadine would provide effective treatment against all circulating influenza viruses. In some instances, oseltamivir alone can still be used, such as when influenza B is diagnosed, or H1N1 viruses are not circulating. It is important to remember that CDC recommends annual influenza vaccination as the first and best step in preventing the flu. It is not too late to get vaccinated and this year′s influenza vaccine is expected to be effective against currently circulating oseltamivir-resistant influenza A (H1N1) viruses.

Helpful relevant links
• Summary of December 19, 2008 Guidance
http://www.cdc.gov/flu/professionals/antivirals/summary.htm
• Full Text of Guidance:
http://www.cdc.gov/flu/professionals/antivirals/index.htm
• Podcast on Influenza Antiviral Resistance and Interim Guidance:
http://www2a.cdc.gov/podcasts/player.asp?f=10652
• Flu activity and surveillance:
http://www.cdc.gov/flu/weekly/fluactivity.htm
• Downloadable high-resolution flu image:
http://www.cdc.gov/media/subtopic/library/diseases.htm
• Flu references and resources:
http://www.cdc.gov/flu/references.htm

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Getting beyond getting ready for pandemic influenza
Report released by the US Department of Homeland Security on 14 Jan 2009

Recognizing that an influenza pandemic would impact US national security and the importance of being ready to handle the pandemic when it occurs, Chairman Thompson and Subcommittee Chairman Langevin directed the Majority Staff to:
• Conduct oversight regarding the pandemic influenza preparedness activities of the Department of Homeland Security (DHS) and other members of the Executive Branch;
• Gather information through hearings, briefings, and meetings to determine the status of national efforts to prepare for pandemic influenza;
• Identify weaknesses in US national preparedness for pandemic influenza; and
• Determine what specific actions could strengthen such efforts and help the nation achieve readiness for pandemic influenza.

The full report of findings and recommendations are available at
http://homeland.house.gov/SiteDocuments/20090114124322-85263.pdf.

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Assessment of States’ Operating Plans to Combat Pandemic Influenza
Report to the Homeland Security Council, January 2009

Statement by Secretary Leavitt and Secretary Chertoff
We are pleased to submit this summary report on States’ operating plans for combating pandemic influenza. Three pandemics occurred during the Twentieth Century – one, in 1918/19, with catastrophic health and socio-economic consequences. The pandemic threat is real and continuing, irrespective of how much the perception of the threat may wax or wane over time. Therefore, if we are to counter the next pandemic effectively, we must prepare now.

This assessment process has done much to increase understanding by State and Federal Government officials alike as to the demands that an influenza pandemic would place upon them. We are grateful to the Working Group from the participating U.S. Government Departments as well as to their State counterparts for undertaking the arduous efforts that this assessment required. Whatever forms future plans and assessments may take, the health and socio-economic well being of the Nation will be well served by a collective commitment to continuous quality improvement in preparing for, responding to, and recovering from an influenza pandemic.

Assessment available at http://pandemicflu.gov/plan/states/state_assessment.html.

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 apecein@u.washington.edu