Would an imperfect vaccine be useful in a flu pandemic?

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Would an imperfect vaccine be useful in a flu pandemic?

Roos News Editor

Apr 11, 2006 (CIDRAP News) – A mathematical modeling study suggests

that a modestly effective vaccine could keep an influenza pandemic

from striking more than 10% of the US population, but only if large

amounts of vaccine were distributed quickly and the virus was not too

highly contagious.

With a more contagious virus, additional measures such as school

closings, travel bans, and antiviral drugs would have to be used in

combination with vaccination, says the report published online last

week by the Proceedings of the National Academy of Sciences.

The modeling study seems to lend some support to the US strategy of

stockpiling a vaccine based on recent strains of H5N1 avian flu,

which won't precisely match an emerging pandemic strain. But the

model incorporates many assumptions that may or may not prove

accurate in the event of a pandemic, and experts note that very

little H5N1 vaccine would be available if a pandemic occurred anytime

soon.

With a moderately transmissible virus (meaning each case leads to

fewer than 1.9 additional cases), " Our model suggests that the rapid

production and distribution of vaccines, even if poorly matched to

the circulating strains, could significantly slow disease spread and

limit the number ill to less than 10% of the population, particularly

if children are preferentially vaccinated, " says the report by

C. Germann and colleagues.

Germann and two associates, Kai Kadau and A. Macken, all of

Los Alamos National Laboratory, worked on the study with Ira M.

Longini Jr., a biostatistician from the Fred Hutchinson Cancer

Research Center and the University of Washington in Seattle.

The study was supported by the National Institutes of Health (NIH).

Its goals, the NIH said in a news release, were to determine how to

slow the spread of a pandemic virus long enough to permit development

and distribution of a well-matched vaccine and also how to limit the

number of cases to less than 10% of the population, the percentage in

an average flu season.

The model simulated the unfolding of pandemic flu in a US population

of 281 million over 180 days. It factored in US census data about

population distribution and commuting patterns and assumptions about

the frequency of interpersonal contacts. It assumed that a few

infected people would arrive from abroad each day at 14 airports in

the United States. The researchers ran the simulations with four

different reproductive ® numbers (the number of additional people

infected by each infected person), ranging from 1.6 to 2.4.

The model projected that without any control effort and an R of 1.9,

the virus would spread across the nation within 30 days of its first

arrivals, that 122 million people would ultimately fall ill, and that

the pandemic would peak in 85 days. With an R number of 2.4 and no

control effort, as many as 151 million would get sick, according to

the model.

" Aggressive " production and distribution of vaccine could control a

pandemic with an R of less than 1.9, the model predicted. " We believe

that a large stockpile of avian-based vaccine with potential pandemic

influenza antigens, coupled with the capacity to rapidly make a

better-matched vaccine based on human strains, would be the best

strategy to mitigate pandemic influenza, " the authors write. " This

effort needs to be coupled with a rapid vaccine distribution system

capable of distributing at least 10 million doses per week to

affected regions of the U.S. "

Other control strategies used alone could limit a pandemic only if

the virus had relatively low transmissibility (R of 1.6), the model

predicted. For example, targeted use of antiviral drugs could succeed

in that case, provided the supply was adequate and close contacts of

patients could be quickly identified. But if R were 1.8, the nation

would need a " prohibitively large " 51 million treatment courses of

antivirals.

For a highly transmissible virus (R greater than 1.9), it would take

a combination of measures to limit the pandemic, the model predicted.

For example, the combined use of vaccination, targeted antiviral use

(3 million courses), school closures, social distancing, and travel

restrictions could work at an R level as high as 2.4, the authors

predict.

Travel restrictions alone would accomplish little, according to the

simulations. A 90% reduction in travel would slow the virus's spread

by only a few days to a few weeks, depending on transmissibility, and

would not dent the ultimate size of the pandemic.

With a very limited supply of a vaccine for which two doses are

recommended, the model showed it would be less helpful to vaccinate a

given number of people with the two doses than to give just one dose

to twice as many people.

Other experts who were asked to comment on the study had different

reactions.

Schaffner, MD, a hospital epidemiologist and professor in the

infectious disease division at Vanderbilt University in Nashville,

said he found the study reassuring, though he had not examined it

closely. " The ultimate take-home line was that even a partially

effective vaccine is an important part of the strategy, " he said.

He added that building up the capacity to treat the sick is

important, but the main emphasis in pandemic preparedness should be

on vaccination and other preventive measures. " The results [of the

study] were so affirming of the general thoughts of the public health

community that it's really very reassuring, and I hope it stimulates

further what I think is already a strong effort by HHS [the

Department of Health and Human Services] to stimulate vaccine

production and research on new ways to produce the flu vaccine and

make better flu vaccines. "

T. Osterholm, PhD, MPH, a leading pandemic preparedness

advocate, had a sharply different view of the study. " I think it's

based on a number of assumptions which in the real world won't

happen, " he said. " The idea that we'll even have vaccine to consider

in terms of dealing with the pandemic is at this point not likely for

the vast majority of the world. "

Osterholm, director of the Universityof Minnesota Center for

Infectious Disease Research and Policy, publisher of the CIDRAP Web

site, said " any number " of assumptions used in the model could be

questioned. " I continue to worry that far too much credence is being

put into theoretical models that lack reality testing in the likely

world of a pandemic, " he said.

Dr. Poland, a vaccine expert at the Mayo Clinic in Rochester,

Minn., said the situation with the H5N1 vaccine being made for the US

government points up the problems with the predictions. As was

reported recently, the vaccine seems effective in about half of

recipients, but it takes 12 times the dose used in seasonal flu

vaccines, he noted.

" A moderately effective vaccine would work if you could get it into

enough people, " said Poland, who directs the Mayo Vaccine Research

Group and Program in Translational Immunovirology. " This current

vaccine, if we used the whole world manufacturing capacity, offers

enough doses for somewhere around 37.5 million people. So that's not

an answer. " He added that it may be necessary to make more than one

vaccine, given the different clades (families) of H5N1 virus that

have emerged.

Poland also said no one knows how contagious the next pandemic virus

will be. " My understanding is that the estimated R number for the

1918 pandemic was right around 3, " higher than the maximum of 2.4

used in the study, he said. " You wonder now if we truly have a novel

subtype that's easily transmissible, given the travel we have, if we

wouldn't have higher numbers. The average family is bigger than two

people. "

http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/apr1106

math.html