Thursday, September 24, 2009

Mass vaccinations for Swine Flu: learning from hindsight

by Australian Infectious Diseases professor Peter Collignon at the ANU:

In 1976, a small group of soldiers at Fort Dix in the US were infected with a swine flu virus. It had an apparent high mortality rate and was deemed similar to the virus responsible for the great 1918-19 worldwide flu pandemic. The US government initiated an unprecedented effort to immunise every American against swine flu. More than 40 million Americans received the vaccine  — but the disease never spread to the population.

The program was marked by controversy, delay, administrative troubles, legal complications, unforeseen side effects and a progressive loss of credibility for public health authorities. One of the biggest issues was the unexpected side effect of ascending paralysis (Guillain-Barré syndrome) that complicated about one in 100,000 people vaccinated and caused 25 deaths.

In the waning days of the flu season, the incoming health secretary asked the Institute of Medicine of the National Academies to examine what happened and to extract lessons to help cope with similar future situations. The result was  The Swine Flu Affair: Decision-Making on a Slippery Disease.

From my perspective, we seem to not have learned much since then. We look to be repeating nearly all the same mistakes  — but this time on a global scale.

I quote verbatim from the summary:

   “Decision-making for the swine flu program had seven leading features.

   To simplify somewhat, they are:

       * Overconfidence by specialists in theories spun from meagre evidence.
       * Conviction fueled by a conjunction of some pre-existing personal agendas.
       * Zeal by health professionals to make their lay superiors do right.
       * Premature commitment to deciding more than had to be decided.
       * Failure to address uncertainties in such a way as to prepare for reconsideration.
       * Insufficient questioning of scientific logic and of implementation prospects.
       * Insensitivity to media relations and the long-term credibility of institutions.”

This time around, we have started from many presumptions that data now shows were wrong. Yet we have not changed our approach. The basis for rolling out a pandemic plan around the world was to be a new flu virus with mortality rates of 1% or more and by a virus that readily spreads from person to person.

While the swine flu virus spreads readily, it has a very low overall mortality rate — less than one per 100,000 of the population and likely less than seasonal flu. It is also likely that more than 10% of the population has already been infected in Australia and New Zealand. The reason this epidemic rapidly decreased after mid-July here, might be because we ran out of further susceptible hosts (as so many had already been infected and are now immune). Thus, the maximum the case fatality rate can be is one per 10,000 infections or 0.01%. Low mortality rates are also seen in data from Canada and the US during their summers.

Original projections and commentary for Australia was that we would see tens of thousands of deaths when this virus spread through an unimmunised population. These have been wrong. Federal Health had one of the lowest of these projections with 6000 deaths by the end of winter. While all deaths are regrettable, in Australia there have been about 170 associated deaths. This number of deaths is much less than the 2000-3000 estimated to occur each winter with seasonal flu here.

Thus, it is unclear to me why we are rushing out in Australia the largest-ever mass vaccination program.

This is with a vaccine that has had less than optimal safety and efficacy studies performed but for which the Government has indemnified CSL. So far the only data available on the CSL PanFlu vaccine has been from a small preliminary study published in the New England Journal of Medicine article about one week ago. It was only based on 220 people and without a comparative placebo arm group. This showed apparent good antibody responses from the vaccine (18-65 year olds). However, it also showed that a third had protective pre-existing antibodies and so were already immune.

About 50% of recipients had systemic or local side effect from the vaccine. In 1%, side effects were severe. This is a much higher rate of adverse events than seen with other inactivated vaccines such as Hepatitis B. We need to also keep in context that the vast majority of people who get swine flu only have a mild-to-moderate illness. Rolling it out in multi-dose vials also has the inherent increased risk of cross infections with bacteria and blood-borne virus infections.

We need to be sure with any vaccination program that the benefits will substantially outweigh the risks. That is not at all clear with this pandemic.

The best up-to-date data that is age-stratified is from NSW Health. It and the other Australian data show now that this flu episode is close to ending (it peaked early and unexpectedly in mid-July). The data show that this flu season has not been much worse overall than 2007 (although certain subgroups e.g. pregnant women have been over-represented in hospital and ICU admissions).

The death rate in the population was low at about 0.8 per 100,000 people.

Overall admission rates were not high either compared to seasonal influenza (17.5 but in previous years about 15 per 100,000). ICU admissions were 3.3 per 100,000 population. There are about 200,000 pregnant women at any one time in Australia. My estimate for death was about two per 100,000 pregnant women. My calculations of deaths by age group are in table 1 of the linked article.

Worldwide we are about to roll out one of the biggest and most rapid vaccine campaigns ever undertaken. Influenza vaccines are not among our most effective vaccines. Reported inactivated vaccine efficacy is 50-80%. Thus at most for every one million people vaccinated we will likely decrease the number of deaths from six to two or three people and prevent 75-120 hospital admissions and 13-22 ICU admissions.

Given the relative lack of infections we are seeing in the elderly, it appears that most people older than  60 are already immune (presumably from previous H1N1 infection). Now also probably at least 30% of 18-65 year olds are already immune and many more have been infected this winter along with those younger than  18. Thus probably much less than 50% of the Australian population may benefit from mass vaccination if H1N1 returns next winter.

We need to weigh this against the risks of vaccination. There will probably be one or two additional episodes of Guillain-Barré syndrome per million vaccine recipients. If we have a repeat of the 1976 US swine flu vaccination roll-out, then there may be 10 cases per million vaccine recipients. We also need to estimate how many bacterial and blood borne virus infections we may expect from the use of multi-use vials.

Australia is now in spring. There is no need here to rush into a mass vaccination program particularly using multi-dose vials. We need to see what happens in the northern hemisphere with the infections and the effects of vaccination.

Some targeted early vaccination in high risk groups may be appropriate in our summer (even though the virus here has substantially disappeared). However, I believe an early mass vaccination program is not appropriate unless we have data that shows the likely benefits will substantially outweigh risks for different age groups.

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