Positive effects of avian (H5N1) influenza
The recent study in Morbidity and Mortality Weekly Report (MMWR. 62:32;2013) that assessed influenza vaccines as being only 62% effective in protecting against influenza is disappointing, but not new information. It is clear from many studies that what we have had is only “moderately effective” and that new and improved vaccines against influenza are needed.
The good news is that the development of new influenza vaccines is flourishing. In just the past year, four influenza vaccines, Flucelvax (Novartis), FluBlok (Protein Sciences), Fluarix (GlaxoSmithKline) Quadrivalent and Fluenz (AstraZeneca) have been approved by the FDA with others on the way.
A number of vaccines are in development, and two of these, assisted with federal funding, are of particular interest. One combines a bacterial protein, flagellin, which is a potent stimulator of the immune system, with influenza viral hemagglutinin. There are other potential vaccines in various stages of research or development including adjuvanted and universal influenza vaccines. A universal influenza vaccine could theoretically be given every 5 to 10 years and protect against most types of influenza including pandemic strains. Most of this group of approved and in-development vaccines use cells or other methods that avoid eggs to manufacture the vaccines. Pharmaceutical companies have not been enthusiastic about expending resources in developing new approaches to development and improvement of influenza vaccines as the vaccines have been expensive to manufacture, the antigens in the viruses in the vaccine vary from season to season and companies can be left with millions of doses that have to be discarded.
Fear of outbreak
Enthusiasm was apparently kindled in 2006, when HHS invested more than $1 billion in contracts to six manufacturers to develop cell-based influenza vaccine technology in the United States. The driving force for this investment was fear of an avian (H5N1) influenza pandemic. Cases were on the rise and there was a fear that mutations could occur that would allow easy person-to-person transmission. There was also a realization that the US had insufficient influenza vaccine manufacturing sites to guarantee enough vaccine to supply its own population in the event of a pandemic. The dependency on production in eggs was seen as an impediment to rapid production of large amounts of vaccine. The egg process is very slow and generally requires huge numbers of fertilized chicken eggs. It is also dependent on the virus growing well in eggs, which occasional strains do not. Periodic lack of adequate supplies of eggs can also be a bottle neck in production.
Details of outbreak
It is of interest to look at what has happened to the H5N1 outbreak, the root cause of what galvanized the thrust into better methods of production as well as improvement of influenza vaccines. Since its recognition in 1997 in Hong Kong, H5N1 has spread in poultry and in wild birds in the Far East and throughout Asia and to parts of the Middle East, Europe and Africa.
Starting in 2003, 610 cases have been reported in humans with 360 deaths. The annual number of deaths over cases has been: 2003 (4/4), 2004 (32/46), 2005 (43/98), 2006 (79/115), 2007 (59/88), 2008 (33/44), 2009 (32/73), 2010 (24/48), 2011 (34/62) and, reported as of Jan. 16, 2013, 2012 (20/32).
Cases have been reported from 15 countries over the years: Indonesia (n=192), Egypt (n=169), Vietnam (n=123), China (n=43), Thailand (n=25), Cambodia (n=21), Turkey (n=12), Azerbaijan (n=8), Bangladesh (n=6), Iraq (n=3), Pakistan (n=3), Laos (n=2), Djibouti (n=1), Nigeria (n=1) and Myanmar (n=1). Of interest is that no new country has been involved since 2008. It also is worth noting that although 15 countries have had cases, only seven countries have had more than 10 cases each. About 80% of the cases have occurred in three countries, Indonesia, Egypt and Vietnam. In recent years, the majority of cases have occurred in Indonesia and Egypt.
H5N1 has been a major disaster in terms of poultry loss and economic damage. However, even allowing for under reporting, the human toll of H5N1 pales compared to the thousands of influenza-associated deaths each year from human influenza in just the US. While anything is possible, it seems unlikely to me that the mutations required for a pandemic will occur with H5N1. The virus has been circulating widely in poultry for at least 10 years. During this time there have been many human exposures in areas where backyard flocks of poultry come in close contact with large numbers of humans (and for that matter swine) on a daily basis. The number of human cases annually peaked at 115 in 2006 and has continued at a lower annual rate ever since. I suspect that if mutations that could allow easy spread from person to person have not occurred by now, they probably never will.
In any event, the federal response to H5N1 has resulted in manufacturing systems that will create the ability to respond more rapidly to any influenza pandemic that may come (including H5N1) and will probably eventually lead to better vaccines.
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Donald Kaye, MD, is a professor of Medicine at Drexel University College of Medicine, Associate Editor of ProMED-mail, Section Editor of News for Clinical Infectious Diseases and is an Infectious Disease News Editorial Board member.Disclosure: Kaye reports no relevant financial disclosures.