Wednesday, November 9, 2005
As you are aware, the potential for a human influenza pandemic is a current public health concern with an immense potential impact. Inter-pandemic (seasonal) influenza causes an average of 36,000 deaths each year in the United States, mostly among the elderly and nearly 200,000 hospitalizations. In contrast, scientists cannot predict the severity and impact of an influenza pandemic, whether from the H5N1 virus currently circulating in Asia and Europe, or the emergence of another influenza virus of pandemic potential. However, modeling studies suggest that, in the absence of any control measures, a “medium-level” pandemic in which 15 percent to 35 percent of the U.S. population develops influenza could result in 89,000 to 207,000 deaths, between 314,000 and 734,000 hospitalizations, 18 to 42 million outpatient visits, and another 20 to 47 million sick people. The associated economic impact in our country alone could range between $71.3 and $166.5 billion. A more severe pandemic, as happened in 1918, could have a much greater impact.
There are several important points to note about an influenza pandemic:
The Current Status of H5N1 Virus in Asia
Almost all cases of H5N1 human infection appear to have resulted from some form of direct or close contact with infected poultry, primarily chickens. In addition, a few persons may have been infected through very close contact with another infected person, but this type of transmission has not led to sustained transmission.
For an influenza virus to cause a pandemic, it must: (1) be a virus to which there is little or no pre-existing immunity in the human population; (2) be able to cause illness in humans; and, (3) have the ability for sustained transmission from person to person. So far, the H5N1 virus circulating in Asia meets the first two criteria but has not yet shown the capability for sustained transmission from person to person.
The avian influenza A (H5N1) epizootic (or animal) outbreak in Asia that is now beginning to spread into Europe is not expected to diminish significantly in the short term. It is likely that H5N1 infection among birds has become endemic in Asia and that human infections resulting from direct contact with infected poultry will continue to occur. So far, scientists have found no evidence for genetic reassortment has been found. Reassortment can occur when the genetic code for high virulence in an H5N1 strain combines with the genetic code of another influenza virus strain which results in easy transmission. However, the animal outbreak continues to pose an important public health threat, because there is little preexisting natural immunity to H5N1 infection in the human population.
In mid-October 2005, I accompanied Secretary Mike Leavitt when he led a delegation of U.S. and international health experts on a 10-day trip to five nations in Southeast Asia. The purpose of this trip was: 1) to learn from countries that have had first-hand experience with avian influenza; 2) to emphasize the importance of timely sharing of information in fighting the disease; and, 3) to determine the best use of our resources abroad to protect people in the United States. We learned several important lessons. First, international cooperation is absolutely essential; an outbreak anywhere increases risk everywhere. Second, surveillance, transparency, and timely sharing of information are critical. The ability of the United States and the world to slow or stop the spread of an influenza pandemic is highly dependent upon early warning of outbreaks. Finally, it is vital to strengthen preparedness and response capabilities in Asian countries and other parts of the world. The delegation also concluded that pandemic preparedness and preparation must be both short– and long--term in scope. These critical elements form the basis of the Administration’s diplomatic engagement strategy through the International Partnership on Avian and Pandemic Flu launched by the President in September, and drive our efforts with the international health community to effectively prepare for a pandemic. As I stated earlier, there is no way to know if the current H5N1 virus will evolve into a pandemic. However, we do know that there have been three pandemics in the past 100 years, and we can expect more in this century.
HHS Role in International Preparedness
In the past year, working with the World Health Organization (WHO) and other international partners HHS and its agencies has made significant progress toward enhancing surveillance in Southeast Asia. However, this initiative needs to continue at both national and international levels if we are to sustain our progress, expand geographic coverage, and conduct effective surveillance. These efforts to build international and domestic surveillance are essential for detecting new influenza virus variants earlier and for making informed vaccine decisions about inter-pandemic influenza. With the ever-present threat of a newly emerging strain that could spark a human pandemic, we need to know what is happening in commercial poultry farms and the family backyard flocks found in Southeast Asia, as well as migrating birds and animal populations elsewhere throughout the world.
Earlier this year, Congress passed and the President signed the Fiscal Year 2005 Emergency Supplemental Appropriations Act for Defense, the Global War on Terror, and Tsunami Relief. This legislation includes $25 million in international assistance funds for HHS, the U.S. Department of Agriculture and the United States Agency for International Development (USAID) to prevent and control the spread of avian influenza in Asia. With these funds, HHS and its agencies are working to assist in developing regional capacity in Southeast Asia for epidemiology and laboratory management of pandemic influenza. Strategies include developing and implementing an avian influenza curriculum for epidemiologists and laboratorians, training for public health leaders to develop a national network of public health field staff, and training for local allied health personnel to detect and report human cases of influenza. HHS is assigning staff are being assigned to Vietnam, Cambodia, and Laos to facilitate improvements in the detection of influenza cases and to provide technical assistance in investigating cases as well as in developing national preparedness plans by the Ministries of Health, with the assistance of WHO and other partners.
We are also working with the U.S. Agency for International Development (USAID) WHO Secretariat, its Regional Offices and Ministries of Health in these countries to increase public awareness about the human health risks associated with pandemic influenza, and to advise countries concerning prevention or mitigation measures that can be used in the event a pandemic occurs.
HHS through CDC is vigorously working to increase laboratory capacity in the region and to provide laboratory support for outbreak investigations, including: a) testing clinical samples and influenza isolates, b) diagnosing the presence of avian influenza in humans by supplying necessary test reagents to the region and globally, and c) developing vaccine seed stock to produce and test pandemic vaccine candidates. The HHS National Institutes of Health (NIH) and Office if Public Health Emergency Preparedness are also providing technical assistance to the Government of Vietnam as it proceeds with the development of a human H5N1 vaccine, including support for clinical trials.
CDC is one of four WHO Global Influenza Collaborating Centers. In this capacity, CDC conducts routine worldwide monitoring of influenza viruses and provides ongoing support for the global WHO surveillance network, laboratory testing, training, and other actions. HHS also supports the WHO Headquarters in Geneva and the WHO Regional Offices in Manila and New Delhi for pandemic planning, expansion of global influenza surveillance, shipment of specimens, training, and enhancing communications with agricultural authorities. Several of the top flu specialists on the WHO staff are HHS personnel on loan, another demonstration of our strong commitment to international collaboration in the fight against the threat of a pandemic influenza.
In addition to our partnership with USAID under the Tsunami supplemental appropriation, HHS also partners with other U.S. Government departments in its international collaboration such as with the Department of Defense Naval Medical Research Unit Two (NAMRU2) in Indonesia and Naval Medical Research Unit Three in Cairo (NAMRU3). These collaborations support training, the expansion of influenza surveillance networks to countries where none exists, the enhancement of the quality of surveillance in other countries to enhance outbreak detection, seroprevalence studies in populations at risk for avian influenza such as poultry workers, and enhanced outbreak response.
Additionally researchers at CDC have conducted studies on the incidence of adamantane resistance among influenza A viruses isolated worldwide from 1994 to 2005. Adamantanes are antiviral drugs that have been used to treat influenza A virus infections for many years. However, their use is rising worldwide, and viral resistance to the drugs has been reported among influenza A viruses (H5N1) strains isolated from poultry and humans in Asia. This data raises questions about the appropriate use of antiviral drugs, especially adamantines, and draws attention to the importance of tracing emergence and spread of drug resistant influenza A viruses. It is important to note that, although at present the H5N1 viruses isolated from people in Asia during the past two years appear to be resistant to adamantanes, they remain sensitive to neuraminidase inhibitors such as oseltamivir (Tamiflu®).
Development and Manufacture of Vaccine
Another important factor is that public demand for influenza vaccine in the United States varies annually. Having a steadily increasing demand would provide companies with a reliable, growing market that would be an incentive to increase their vaccine production capacity. In FY 2006, CDC will direct $40 million through the Vaccines for Children (VFC) program to purchase influenza vaccine for the national pediatric stockpile as additional protection against annual outbreaks of influenza. These funds to purchase vaccine can be used if needed during annual influenza seasons or possibly in a pandemic situation. HHS has also signed a $100 million contract with sanofi pasteur to develop cell culture vaccines. In addition, the President is requesting $120 million in FY 2006, an increase of $21 million, to encourage greater production capacity that will enhance the U.S.-based vaccine manufacturing surge capacity to help prepare for a pandemic and further guard against annual shortages.
Funds from the Strategic National Stockpile (SNS) have purchased approximately two million bulk doses of unfinished, unfilled H5N1 vaccine. This vaccine has not yet been formulated into vials, nor is the vaccine licensed by the HHS Food and Drug Administration. Clinical testing to determine dosage and schedule for this vaccine began in April 2005 with funding from NIH. Initial testing shows that, in its current form, a much higher volume of vaccine, up to 12 times as much as originally predicted, will be needed to produce the desired immune response in people. HHS therefore is supporting the development and testing of potential dose-sparing strategies that could allow a given quantity of vaccine stock to be used in more people. These strategies include developing adjuvants, substances added to a vaccine to aid its action, and the possibility of using intradermal rather than intramuscular injections. Such studies are currently underway, funded through the NIH. Additionally, HHS recently announced the award of a contract to the Chiron Corporation for the development of an H5N1 vaccine.
One of the main efforts by HHS in pandemic preparedness is to expand the nation’s use of influenza vaccine during inter-pandemic influenza seasons. This increase will help assure that the United States is better prepared for a pandemic. Influenza vaccine demand drives influenza vaccine supply. As we increase annual production efforts, this should strengthen our capacity for vaccine production during a pandemic. We are also developing strategies to increase influenza vaccine demand and access by persons who are currently recommended to receive vaccine each year.
In addition to outlining the federal response in terms of vaccines, surveillance, and planning, the HHS Pandemic Influenza plan makes clear the role of individual Americans in the event of an influenza pandemic. The importance of such ordinary but simple steps as frequent hand washing, containing coughs and sneezes, keeping sick children (and adults) home until they are fully recovered are widely seen as practical and useful for helping control the spread of infection. The plan also describes options for social-distancing actions, such as “snow days” and alterations in school schedules and planned large public gatherings. While such measures are, ordinarily, unlikely to fully contain an emerging outbreak, they may help slow the spread within communities.
State and Local Preparedness and Planning
CDC is working to: (1) ensure that states have sufficient epidemiologic and laboratory capacity both to identify novel viruses throughout the year and to sustain surveillance during a pandemic; (2) improve reporting systems so that information needed to make public health decisions is available quickly; (3) enhance systems for identifying and reporting severe cases of influenza; (4) develop population-based surveillance among adults hospitalized with influenza; and, (5) enhance monitoring of resistance to current antiviral drugs to guide policy for use of scarce antiviral drugs.
Collaboration with the Council for State and Territorial Epidemiologists (CSTE) has considerably improved domestic surveillance through making pediatric deaths associated with laboratory-confirmed influenza nationally notifiable, and by implementing hospital-based surveillance for influenza in children at selected sites. CDC will continue to work with CSTE to make all laboratory confirmed influenza hospitalizations notifiable. Since 2003, interim guidelines have been issued to states and hospitals for enhanced surveillance to identify potential H5N1 infections among travelers from affected countries, and these enhancements continue. Special laboratory training courses to teach state laboratory staff how to use molecular techniques to detect avian influenza have been held. In the past year, CDC trained professionals from all 48 states that desired training.
CDC has developed, with input from state and local health departments, and healthcare partners, guidance that provides healthcare facilities with recommendations for developing plans to respond to an influenza pandemic and guidance on the use of appropriate infection control measures to prevent transmission during patient care. Development of and participation in tabletop exercises over the past two years have identified gaps and provided recommendations for healthcare facilities to improve their readiness to respond and their integration in the overall planning and response efforts of their local and state health departments. The healthcare system has made great strides in preparation for a possible pandemic, but additional planning still needs to occur.
Enhancement of Quarantine Stations
HHS and the Department of Homeland Security (DHS) have recently concluded a Memorandum of Understanding setting out the roles and responsibilities of the two agencies. DHS will assist in keeping communicable diseases from entering the U.S. borders; HHS/CDC will be providing training and other necessary support and helping to prevent disease from entering the U.S.
Informing the Public
The outbreaks of avian influenza in Asia and Europe have highlighted several gaps in global disease surveillance that the United States must address in conjunction with partnering nations. These limitations include: 1) insufficient infrastructure in many countries for in-country surveillance networks; 2) the need for better training of laboratory, epidemiologic, and veterinary staff; and, 3) the resolution of longstanding obstacles to rapid and open sharing of surveillance information, specimens, and viruses among agriculture and human health authorities in affected countries and the international community. The International Partnership the President established is also looking at how best to solve these challenges.
During an influenza pandemic, the presence of influenza vaccine manufacturing facilities in the United States will be critically important. The pandemic influenza vaccines produced in other countries are unlikely to be available to the U.S. market, because those governments have the power to prohibit export of the vaccines until their domestic needs are met. The U.S. vaccine supply is particularly fragile. Only one of four influenza vaccine manufacturers selling vaccine in the U.S. market makes its vaccine entirely in this country. It is necessary to ensure an enhanced and stable domestic influenza vaccine market to assure both supply and demand.
Although the present avian influenza H5N1 strain in Southeast Asia does not yet have the capability of sustained person-to-person transmission, we are concerned that it could develop this capacity. CDC is closely monitoring the situation in collaboration with WHO, the affected countries, and other partners. We are using its extensive network with other federal agencies, provider groups, non-profit organizations, vaccine and antiviral manufacturers and distributors, and state and local health departments to enhance pandemic influenza planning. Additionally, the national response to the annual domestic influenza seasons provides a core foundation for how the nation will face and address pandemic influenza.
Thank you for the opportunity to share this information with you. I am happy to answer any questions.
Last Revised: November 10, 2005