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17 September 2005 |
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US to stockpile second drug (zanamivir) to treat H5N1 influenza, add $100 million worth of H5N1 vaccine, and travel to SE Asia in October. |
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The Secretary of the US Health and Human Services (HHS), Mike Leavitt, announced in a news release September 15that the US will augment the Strategic National Stockpile (SNS) with both drug and vaccine countermeasures for the H5N1 influenza virus spreading across Asia (www.hhs.gov/news/press/2005pres/20050915.html). |
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So far, the oral (capsule for adults, liquid for children) anti-influenza drug oseltamivir (“Tamiflu”) has been added to the SNS in quantities sufficient to treat 2.3 million persons (i.e., two capsules each day for 5 days as standard regimen for any type of influenza). Now the US will add a 2nd anti-H5N1 influenza drug, zanamivir (“Relenza”), to the SNS by awarding a $2.8 million contract to purchase quantities sufficient to treat 84,300 persons. |
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Importantly, however, no oral form of zanamivir exists and it is not FDA-licensed for prophylaxis of persons of any age. Instead, zanamivir is FDA-licensed only as a treatment for active influenza disease, and comes in an inhaled preparation only. The drug is given twice each day for five (5) days via a breath-activated plastic device called a Diskhaler (according to the FDA website description of the drug at www.fda.gov/cder/news/relenza/default.htm). Like oseltamivir, zanamivir acts as a neuraminidase inhibitor of influenza viruses. |
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Of note, persons with asthma and chronic lung diseases should generally not use zanamivir due to the risk of exacerbating breathing problems (according to the FDA). Zanamivir is FDA-licensed for persons down to the age of seven (7) years. |
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The other neuraminidase inhibitor anti-flu drug, oseltamivir (“Tamiflu”) is FDA-licensed as an early (within 48 hours of symptoms) therapy for influenza down to the age of one (1) year, and for prophylaxis in persons down to the age of 13 years. Thus, no drug is FDA-licensed for the prophylaxis of influenza in persons less than 13 years of age. |
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The other countermeasure against H5N1 that was purchased is an investigational vaccine to be made by the company Sarnoff Pasteur, according to the HHS news release. Exactly how many persons can be vaccinated with this $100 million worth of vaccine is unclear, because the final amount of vaccine antigen in each dose has yet to be determined. So far clinical trials in the USA (U. of Maryland, U. of Rochester, and UCLA), funded by the NIAID/NIH, have shown presumably protective levels of an immune response against the H5N1 virus currently circulating in Asia only at the highest dose tested, namely 90 micrograms, and even then only after two (2) shots of the vaccine several weeks apart. In contrast, the usual annual flu vaccine requires only 15 micrograms, and only one shot, to achieve a protective immune response. |
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This current H5N1 vaccine does not contain a “vaccine adjuvant”, i.e., a chemical substance such as the FDA-licensed adjuvant called “alum” (e.g., aluminum hydroxide) that stimulates a stronger immune response (in the case of alum more antibody-based immunity than cell-mediated immunity) for a given level of vaccine antigen. |
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Future vaccines against H5N1 might study at least two “antigen-sparing” approaches to increase the amount of H5N1 antigen available to vaccinate more people. One “antigen-sparing” approach is to add a vaccine adjuvant such as alum or investigational adjuvants such as MF-59 or other candidate adjuvants, to the H5N1 vaccine. A second approach could be to give the vaccine under the skin (“subcutaneously”) rather than into the muscle (e.g., of the upper arm or “deltoid” muscle) to see if a stronger immune response is induced against H5N1 when the vaccine is introduced to the immune system sentinel cells (“antigen-processing cells”) under the skin than in the muscle tissue. Some precedent for this approach exists with influenza virus strains other than H5N1. |
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In addition, HHS Secretary Leavitt also announced on September 15th at the UN General Assembly US participation in the International Partnership on Avian and Pandemic Influenza. He will be leading a delegation from the US to Vietnam, Thailand, Cambodia, and Laos next month (October) to meet with Heads of State and Ministers of Health. He has invited the WHO Director-General, Dr. Lee, the Heads of the UN Food and Agricultural Organization (FAO) and the World Animal Health Organization (OIE—French acronym), and the US State Department Under Secretary Dobriansky to join him. The US Congress has approved funding to assist with H5N1 surveillance and other efforts in some affected parts of Asia. |
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Secretary Leavitt stated in his presentation to the UN General Assembly: “Here in the United States, we have adopted a simple rule for our preparedness: prepare as if the pandemic strikes tomorrow…We’ve all learned in the past few weeks, that bad things can happen very fast. This is why the new International Partnership on Avian and Pandemic Influenza is so critical. We simply must improve global readiness in an unprecedented way.” (www.hhs.gov/news/press/2005pres/20050915a.html). |
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Daniel R. Lucey, MD, MPH |
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Adjunct Professor of Microbiology and Immunology |
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Georgetown University School of Medicine |
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Director, Center for Biological Counterterrorism and Emerging Diseases |
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Department of Emergency Medicine, Washington Hospital Center |
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Washington, DC |
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Website: www.BePast.org; e-mail: Daniel.R.Lucey@Medstar.net |