31 August 2004

 

The US Pandemic Influenza Plan: Just in Time?

 

            On August 26 the US Department of Health and Human Services released the draft Pandemic Influenza Preparedness and Response Plan. This plan is timely.  Only the next few years will determine how timely.

            Reports confirmed by the World Health Organization (WHO) in the past two months document that the avian influenza A H5N1 virus has killed at least three more persons in Vietnam, has been found in poultry in at least five nations in Asia, and was detected in pigs in China in 2003-2004.

            The significance of pigs being infected with H5N1 is that in the past other pigs have also been shown to be infected with human influenza A virus H3N2. Thus, the risk is evident of a novel hybrid, or reassortant influenza virus forming in pigs that are infected both with an avian influenza (such as H5N1) and a human influenza virus (such as H3N2).  If such a novel virus spreads readily from person-to-person and was so different that the human population had no prior immunity from past similar infections or similar vaccines, then by definition a “pandemic influenza” crisis could occur.

            The timeliness of this new Pandemic Influenza Plan is not related only to the evolving avian influenza H5N1 virus. In fact, “bird flu” H5N1 is only one of several candidate pandemic influenza viruses, along with H9N2, H7N7, and H7N2 that have been reported within the past two years to infect humans.  These infections of humans have been in small numbers due to little or no person-to-person spread. Thus, no pandemic influenza has occurred.

            The widespread infection of poultry in 2004 by avian influenza H5N1 in some parts of Asia is unprecedented and unlikely to be eradicated in the immediate future. Thus, preparing in earnest now for pandemic influenza in humans is critical, even though no pandemic has begun yet. The past century saw three pandemics: 1918, 1957, and 1968.

 

            Four key points, of many, that can be emphasized from an initial reading of the 55 page core draft plan and 12 additional annexes include:

 

1.       The six pandemic phases of the plan (see annex 1, page 21) are the same as the WHO pandemic staging system.  These phases range from “Phase 0” (the current inter-pandemic phase) to “Phase 5” (confirmation that the pandemic waves have ended).  We are currently in “Level 2” of Phase 0 defined by the recognition of novel influenza viruses (such as H5N1 and others above) that infect humans without causing widespread person-to-person spread.

2.       Unlike the SARS or smallpox viruses, which usually do not spread from person-to-person before symptoms occur, humans infected with influenza virus can shed virus and potentially infect other people before becoming asymptomatic, as well as during asymptomatic influenza infections. This fact, along with others, will likely make infection control, isolation, and quarantine more difficult during pandemic influenza (annex 8, page 7).

3.       Unlike the yearly human flu vaccines that require only one dose for adults, the new vaccines that would be required to protect against a pandemic influenza virus might need two (2) doses, spaced several weeks apart. Thus, a computerized tracking system and ability to give the 2^nd dose on time would be critical (annex 6, page 7).  A 2^nd dose of vaccine might be required since there may be no prior human immunity, due to either infection or vaccination, against such a novel virus.   

4.       Of the two classes of anti-influenza drugs, the adamantines (amantadine and rimantadine) “may be the preferred choice for prophylaxis if the pandemic strain is susceptible”. The second class of drugs, the neuraminidase inhibitors (oseltamivir (oral) and zanamivir (inhaled) “may be the preferred choice for treatment (annex 7, page 8). However, only limited amounts of oseltamivir are available. In addition, H5N1 viral isolates from patients in early 2004 in Vietnam were resistant to amantadine and rimantadine, the older and less expensive anti-influenza drugs, but still sensitive to oseltamivir, the only oral neuraminidase inhibitor.