Dose of Pre-Pandemic Influenza Vaccines to Reduce the Infection Attack Rate

[sharon sanders]

Optimizing the Dose of Pre-Pandemic Influenza Vaccines to Reduce the Infection Attack Rate

<!-- end title area --> <!-- start authors --> Steven Riley^*, Joseph T. Wu, Gabriel M. Leung
<!-- end authors --> <!-- start affiliations --> 1 Department of Community Medicine and School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
<!-- end affiliations --><!-- start: abstract --> Background
The recent spread of avian influenza in wild birds and poultry may be a precursor to the emergence of a 1918-like human pandemic. Therefore, stockpiles of human pre-pandemic vaccine (targeted at avian strains) are being considered. For many countries, the principal constraint for these vaccine stockpiles will be the total mass of antigen maintained. We tested the hypothesis that lower individual doses (i.e., less than the recommended dose for maximum protection) may provide substantial extra community-level benefits because they would permit wider vaccine coverage for a given total size of antigen stockpile.
Methods and Findings
We used a mathematical model to predict infection attack rates under different policies. The model incorporated both an individual's response to vaccination at different doses and the process of person-to-person transmission of pandemic influenza. We found that substantial reductions in the attack rate are likely if vaccines are given to more people at lower doses. These results are applicable to all three vaccine candidates for which data are available. As a guide to the magnitude of the effect, we simulated epidemics based on historical studies of immunogenicity. For example, for one of the vaccines for which data are available, the attack rate would drop from 67.6% to 58.7% if 160 out of the total US population of 300 million were given an optimal dose rather than 20 out of 300 million given the maximally protective dose (as promulgated in the US National Pandemic Preparedness Plan). Our results are conservative with respect to a number of alternative assumptions about the precise nature of vaccine protection. We also considered a model variant that includes a single high-risk subgroup representing children. For smaller stockpile sizes that allow vaccine to be offered only to the high-risk group at the optimal dose, the predicted benefits of using the homogenous model formed a lower bound in the presence of a risk group, even when the high-risk group was twice as infective and twice as susceptible.
Conclusions
In addition to individual-level protection (i.e., vaccine efficacy), the population-level implications of pre-pandemic vaccine programs should be considered when deciding on stockpile size and dose. Our results suggest that a lower vaccine dose may be justified in order to increase population coverage, thereby reducing the infection attack rate overall.

<!-- end abstract --> <!-- start footnote section -->Funding: This work was supported by grants from the Research Fund for the Control of Infectious Diseases of the Health, Welfare and Food Bureau of the Hong Kong SAR Government (JTW, SR, GML); and The University of Hong Kong SARS Research Fund (SR, GML).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
Academic Editor: Marc Lipsitch, Harvard School of Public Health, United States of America
Citation: Riley S, Wu JT, Leung GM (2007) Optimizing the Dose of Pre-Pandemic Influenza Vaccines to Reduce the Infection Attack Rate. PLoS Med 4(6): e218 doi:10.1371/journal.pmed.0040218
Received: November 1, 2006; Accepted: June 11, 2007; Published: June 19, 2007
Copyright: ? 2007 Riley et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abbreviations: HI, haemagglutinin inhibition; HPAI, highly pathogenic avian influenza
* To whom correspondence should be addressed. E-mail: steven.riley@hku.hk
These authors contributed equally to this work.

http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0040218

[gsgs]

Re: Dose of Pre-Pandemic Influenza Vaccines to Reduce the Infection Attack Rate

they want 20million double-doses of prepandemic vaccine by end
of 2008 and pay $1.6e9 for it or about $80 per double-dose.
(Switzerland paid about $25 per dose, only one dose required)
Maybe they have to rotate,
because the old vaccine is expired by then.
Actually they have about 7 million double-doses.

Now in a 1918-like pandemic (they say 1918-like , but assume R0=1.8)
they would save 27 million infections (67&#37; attack-rate , is it
serological attack rate ? cumulative over 3 waves ?)
per year using that vaccine.

That's about $60 per saved infection or $600 worth of a
prevented infection as expection value when we assume 10%
probability of a pandemic per year.

with a CFR of 1% from these 67% as in 1918, we'd expect
2 million deaths, just assume this is reduced also by 9% as
the attack rate, that gives 180000 spared deaths
or -assuming 2% probability per year for a 1918-like pandemic
and ignoring other pandemics - gives $180000 worth per
saved life. The probabilities are about what the actuaries estimate.
This second calulation ignores morbidity, so sickness without death
is ignored, taking that also into account gives probably
less than $100000 worth per expected saved life

---------------
1e9 = 1*10^9 = 1000000000 (pocket calculator notation)
double-dose means, that 2 vaccinations are required, typically 3 weeks apart,
one double dose is enough for both vaccination.