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Of Ducks and Men

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F. Edward Yazbak MD

 

According to the CDC, “Manufacturers have begun shipping flu vaccines for the 2013-2014 US Season. Between 135 million and 139 million doses of vaccine are being produced. While some vaccine will be available in August, ample supplies should be available by September and October. Everyone 6 months of age and older should get their yearly flu vaccine, ideally by October.” http://www.cdc.gov/flu/ (8/28/13)

Everything the CDC wants us to know about seasonal influenza vaccination can be found at http://www.cdc.gov/flu/protect/keyfacts.htm

The following are the CDC’s “Primary Changes and Updates in the Recommendations” for now:

  • Routine annual influenza vaccination of all persons aged 6 months and older continues to be recommended.
  • 2013-14 U.S. trivalent influenza vaccines will contain an A/California/7/2009 (H1N1)-like virus, an H3N2 virus antigenically like the cell-propagated prototype virus A/Victoria/361/2011, and a B/Massachusetts/2/2012-like virus. Quadrivalent vaccines will include an additional vaccine virus, a B/Brisbane/60/2008-like virus.
  • Several new, recently-licensed vaccines will be available for the 2013-14 season, and are acceptable alternatives to other licensed vaccines indicated for their respective age groups when otherwise appropriate:
    • A quadrivalent live attenuated influenza vaccine (LAIV4; Flumist® Quadrivalent [MedImmune]) is expected to replace the trivalent (LAIV3) formulation. FluMist® Quadrivalent is indicated for healthy, nonpregnant persons aged 2 through 49 years;
    • A quadrivalent inactivated influenza vaccine (IIV4; Fluarix® Quadrivalent [GlaxoSmithKline]) will be available, in addition to the previous trivalent formulation. Fluarix® Quadrivalent is indicated for persons aged 3 years and older;
    • A quadrivalent inactivated influenza vaccine (IIV4; Fluzone® Quadrivalent [Sanofi Pasteur]) will be available in addition to the previous trivalent formulation. Fluzone® Quadrivalent is indicated for persons aged 6 months and older;
    • A trivalent cell culture-based inactivated influenza vaccine (ccIIV3; Flucelvax® [Novartis]), which is indicated for persons aged 18 years and older; and
    • A recombinant hemagglutinin (HA) vaccine (RIV3; FluBlok® [Protein Sciences]), which is indicated for persons aged 18 through 49 years.
  • Within approved indications and recommendations, no preferential recommendation is made for any type or brand of licensed influenza vaccine over another.                                                          http://www.cdc.gov/flu/professionals/acip/2013-summary-recommendations.htm

Although it appears that we are still fortunate to have escaped the addition of a “Bird Flu” strain to our “seasonal influenza vaccine” this year, there is ample reason to believe that like taxes and death, this is eventually going to catch up with us. In fact, today’s CDC Influenza Home Page carries not one but two items on the subject, often a subtle signal that a vaccine is not too far in the future. In the first, the CDC lists information on the bird illness in general and in the second, it announces the arrival of another “NEW” Avian (H7N9) Influenza A Virus. http://www.cdc.gov/flu/

H7N9 is not the subject of this commentary. It will be a long while before we know enough about it and about its issues and problems. On the other hand, H5N1, the original bird flu strain has provided us already with important and valuable information that needs serious attention and prompt consideration.

The following by Sims, Domenech, Benigno et al of the Italian FAO Animal Health Service seems to be the best available historical review of H5N1 influenza infections:

“Outbreaks of highly pathogenic avian influenza caused by H5N1 viruses were reported almost simultaneously in eight neighbouring Asian countries between December 2003 and January 2004, with a ninth reporting in August 2004, suggesting that the viruses had spread recently and rapidly… Possible explanations include limited virus excretion by domestic waterfowl infected with H5N1, the confusion of avian influenza with other serious endemic diseases, the unsanctioned use of vaccines, and the under-reporting of disease as a result of limited surveillance…Asian H5N1 viruses were first detected in domestic geese in southern China in 1996. By 2000, their host range had extended to domestic ducks, which played a key role in the genesis of the 2003/04 outbreaks. The epidemic was not due to the introduction and spread of a single virus but was caused by multiple viruses which were genotypically linked to the Goose/GD/96 lineage via the haemagglutinin gene. The H5N1 viruses isolated from China, including the Hong Kong SAR, between 1999 and 2004 had a range of genotypes and considerable variability within genotypes…[PMID: 16085721] -2005

A review titled “Vaccination of domestic ducks against H5N1 HPAI” was just published on August 3, 2013 in “Vaccine Research” (Elsevier B.V.) The authors, all from the “Exotic and Emerging Avian Viral Diseases Unit, Southeast Poultry Research Laboratory, U.S. DOA - Agricultural Research Service” in Athens GA reported the following:

  • Domestic ducks play an important role in the epidemiology of H5N1 highly pathogenic avian influenza (HPAI) viruses.
  • Consequently, successful control of H5N1 HPAI in ducks is important for the eradication of the disease in poultry and ultimately the prevention of serious human disease.
  • Domestic ducks include different species and the susceptibility to infection, disease and response to vaccination can vary depending on the species and age of the bird.
  • Current vaccines and vaccination practices are insufficient for the control of H5N1 HPAI virus infections in domestic waterfowl and new vaccination strategies are needed.
  • Although vaccination has proven effective in protecting ducks against disease, shedding of the virus still occurs in clinically healthy vaccinated populations. [PMID: 23916865] -2013

The above findings supported and confirmed research by the same Athens GA group that was published in “Vaccine” (Elsevier B.V.) in 2011 under the title: “Pekin and Muscovy ducks respond differently to vaccination with a H5N1 highly pathogenic avian influenza (HPAI) commercial inactivated vaccine.”

Suspected of being intermediate hosts in the transmission of the virus, domestic ducks had been included in the planned vaccination programs to control H5N1 HPAI.

The 2011 research showed that vaccination had been effective but that virus shedding was still occurring among the healthy vaccinated populations. It also demonstrated that the response to vaccination between the two common domestic duck species, Pekin (Anas platyrhynchos domesticus) and Muscovy (Cairina moschata) was strikingly different: Muscovy ducks developed lower viral antibody titers and presented with higher morbidity and mortality after challenge with an H5N1 HPAI virus.

When comparing the response to infection in non-vaccinated ducks, infected Muscovy ducks had a lower mean death time and exhibited more severe neurological signs than Pekin ducks. Pekin ducks on the other hand had significantly higher body temperatures and higher levels of nitric oxide in the blood at 2 days post challenge than Muscovy ducks, suggesting differences in innate immune responses.

At the time, the researchers also reported that among non-vaccinated infected ducks, Pekin ducks had significantly higher levels of expression of RIG-I while Muscovy ducks had higher expression of IL-6. Both duck species showed an up-regulation of IFNα and MHC-I expression, and a down-regulation of MHC-II.

Having convincingly shown that the two domestic duck species had differences in response to infection and vaccination, the authors wisely recommended that their findings be considered when developing effective vaccination programs for controlling H5N1 HPAI in different species of ducks. 

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Important vaccine research at the Athens GA Southeast Poultry Research Laboratory was likely accelerated by the culling of 200 million birds in Asia in 2005. Even though our US researchers were clearly excited about the new vaccines they remained objective and honest about their limitations. They were happy to announce that potent Avian Influenza vaccines “when properly used can prevent disease and death, increase resistance to infection, reduce field virus replication and shedding, and reduce virus transmission” but they were also not afraid to add that the vaccines “do not provide "sterilizing immunity" in the field; i.e., vaccination does not completely prevent AI virus replication.” [PMID: 17135509]-2006

Atlanta is only 70 miles from Athens. Now if we could convince the CDC experts in Atlanta to talk to their counterparts in Athens, may be they could learn something and may be we would all be better off when and if “human” Bird Flu arrives.  

After all, may be? what is good for a duck is good for a baby!

 

F. Edward Yazbak, MD, Falmouth MA

9-4-2013